Combinations of diagnostic or therapeutic substances linked with specific immune substances such as IMMUNOGLOBULINS; MONOCLONAL ANTIBODIES; or ANTIGENS. Often the diagnostic or therapeutic substance is a radionuclide. These conjugates are useful tools for specific targeting of DRUGS and RADIOISOTOPES in the CHEMOTHERAPY and RADIOIMMUNOTHERAPY of certain cancers.
Semisynthetic conjugates of various toxic molecules, including RADIOACTIVE ISOTOPES and bacterial or plant toxins, with specific immune substances such as IMMUNOGLOBULINS; MONOCLONAL ANTIBODIES; and ANTIGENS. The antitumor or antiviral immune substance carries the toxin to the tumor or infected cell where the toxin exerts its poisonous effect.
An ansa macrolide isolated from the MAYTENUS genus of East African shrubs.
Blood proteins whose activities affect or play a role in the functioning of the immune system.
A class of organic compounds containing a ring structure made up of more than one kind of atom, usually carbon plus another atom. The ring structure can be aromatic or nonaromatic.
Unstable isotopes of yttrium that decay or disintegrate emitting radiation. Y atoms with atomic weights 82-88 and 90-96 are radioactive yttrium isotopes.
Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (IMMUNOTOXINS) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (see RADIOTHERAPY).
Antibodies produced by a single clone of cells.
A protein phytotoxin from the seeds of Ricinus communis, the castor oil plant. It agglutinates cells, is proteolytic, and causes lethal inflammation and hemorrhage if taken internally.
Unstable isotopes of copper that decay or disintegrate emitting radiation. Cu atoms with atomic weights 58-62, 64, and 66-68 are radioactive copper isotopes.
Ring compounds having atoms other than carbon in their nuclei. (Grant & Hackh's Chemical Dictionary, 5th ed)
Unstable isotopes of indium that decay or disintegrate emitting radiation. In atoms with atomic weights 106-112, 113m, 114, and 116-124 are radioactive indium isotopes.
Partial immunoglobulin molecules resulting from selective cleavage by proteolytic enzymes or generated through PROTEIN ENGINEERING techniques.
Transplantation between animals of different species.
Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.
Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection.
Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.
Experimental transplantation of neoplasms in laboratory animals for research purposes.
Drugs that are pharmacologically inactive but when exposed to ultraviolet radiation or sunlight are converted to their active metabolite to produce a beneficial reaction affecting the diseased tissue. These compounds can be administered topically or systemically and have been used therapeutically to treat psoriasis and various types of neoplasms.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.
A cell line derived from cultured tumor cells.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
Established cell cultures that have the potential to propagate indefinitely.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.

67Cu-2IT-BAT-Lym-1 pharmacokinetics, radiation dosimetry, toxicity and tumor regression in patients with lymphoma. (1/1300)

Lym-1, a monoclonal antibody that preferentially targets malignant lymphocytes, has induced therapeutic responses and prolonged survival in patients with non-Hodgkin's lymphoma when labeled with 1311. Radiometal-labeled antibodies provide higher tumor radiation doses than corresponding 1311 antibodies. 67Cu has an exceptional combination of properties desirable for radioimmunotherapy, including gamma and beta emissions for imaging and therapy, respectively, a biocompatible half-time and absence of pathways contributing to myelotoxicity. The radioimmunoconjugate, 67Cu-21T-BAT-Lym-1, has been shown to be efficacious in nude mice bearing human Burkitt's lymphoma (Raji) xenografts. Based on these results, a clinical study of the pharmacokinetics and dosimetry of 67Cu-21T-BAT-Lym-1 in patients with lymphoma was initiated. METHODS: Eleven patients with advanced stage 3 or 4 lymphoma were given a preload dose of unmodified Lym-1, then an imaging dose of 126-533 MBq (3.4-14.4 mCi) 67Cu-21T-BAT-Lym-1. Total Lym-1 ranged from 25 to 70 mg dependent on the specific activity of the radioimmunoconjugate and was infused at a rate of 0.5-1 mg/min. Imaging, physical examination, including caliper measurement of superficial tumors, and analysis of blood, urine and fecal samples were performed for a period of 6-13 d after infusion to assess pharmacokinetics, radiation dosimetry, toxicity and tumor regression. RESULTS: In 7 patients, in whom superficial tumors had been accurately measured, tumors regressed from 18% to 75% (mean 48%) within several days of 67Cu-21T-BAT-Lym-1 infusion. The uptake and biological half-time of 67Cu-21T-BAT-Lym-1 in tumors were greater than those of normal tissues, except the mean liver half-time exceeded the mean tumor half-time. The mean tumor-to-marrow radiation ratio was 32:1, tumor-to-total body was 24:1 and tumor-to-liver was 1.5:1. Images were of very good quality; tumors and normal organs were readily identified. Mild and transient Lym-1 toxicity occurred in 6 patients; 1 patient developed a human antimouse antibody. There were no significant changes in blood counts or serum chemistries indicative of radiation toxicity. CONCLUSION: Because of the long residence time of 67Cu-21T-BAT-Lym-1 in tumors, high therapeutic ratios were achieved and, remarkably, numerous tumor regressions were observed after imaging doses. The results indicate considerable therapeutic potential for 67Cu-21T-BAT-Lym-1.  (+info)

The CTLA-4 gene is expressed in placental fibroblasts. (2/1300)

In order to elucidate the mechanisms that ensure survival of the allogeneic fetus, we are investigating the expression pattern of genes that are involved in peripheral self-tolerance in tissues at the maternal-fetal interface. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a negative regulator of T cell activation and may modulate peripheral self-tolerance. Previously, we reported the preferential transmission of maternally-inherited shorter alleles at a 3'-UTR microsatellite locus to liveborn children, but random transmission of paternally-inherited alleles, suggesting that CTLA-4 may be involved in the maintenance of tolerance at the maternal-fetal interface. In this report, we demonstrate that CTLA-4 mRNA and protein are indeed expressed in fetal tissues at the maternal-fetal interface throughout gestation.  (+info)

Cellular and molecular characterization of the scurfy mouse mutant. (3/1300)

Mice hemizygous (Xsf/Y) for the X-linked mutation scurfy (sf) develop a severe and rapidly fatal lymphoproliferative disease mediated by CD4+CD8- T lymphocytes. We have undertaken phenotypic and functional studies to more accurately identify the immunologic pathway(s) affected by this important mutation. Flow cytometric analyses of lymphoid cell populations reveal that scurfy syndrome is characterized by changes in several phenotypic parameters, including an increase in Mac-1+ cells and a decrease in B220+ cells, changes that may result from the production of extremely high levels of the cytokine granulocyte-macrophage CSF by scurfy T cells. Scurfy T cells also exhibit strong up-regulation of cell surface Ags indicative of in vivo activation, including CD69, CD25, CD80, and CD86. Both scurfy and normal T cells are responsive to two distinct signals provided by the TCR and by ligation of CD28; scurfy cells, however, are hyperresponsive to TCR ligation and exhibit a decreased requirement for costimulation through CD28 relative to normal controls. This hypersensitivity may result, in part, from increased costimulation through B7-1 and B7-2, whose expression is up-regulated on scurfy T cells. Although the specific defect leading to this hyperactivation has not been identified, we also demonstrate that scurfy T cells are less sensitive than normal controls to inhibitors of tyrosine kinases such as genistein and herbimycin A, and the immunosuppressant cyclosporin A. One interpretation of our data would suggest that the scurfy mutation results in a defect, which interferes with the normal down-regulation of T cell activation.  (+info)

Experimental murine schistosomiasis in the absence of B7 costimulatory molecules: reversal of elicited T cell cytokine profile and partial inhibition of egg granuloma formation. (4/1300)

The granulomatous inflammation in infection with the helminth Schistosoma mansoni represents a cellular hypersensitivity reaction mediated by, and dependent upon, MHC class II-restricted CD4+ Th cells sensitized to parasite egg Ags. The current work examines the role and significance of the B7:CD28/CTLA-4 pathway in providing the costimulation necessary for the activation of these pathogenic T cells. In vitro T cell responses in B7-1-/- mice, 7-8 wk postinfection, were no different from wild-type controls, but the absence of B7-2 molecules resulted in a decrease in egg Ag-induced proliferation with increased IFN-gamma production. Both B7-1-/- and B7-2-/- mice exhibited intact granuloma formation. In contrast, CD4+ Th cells from B7-1/2 double-deficient mice displayed a dramatic loss of proliferative capacity upon stimulation with egg Ag. Most strikingly, these T cells secreted only IFN-gamma, but not IL-4 and IL-10, a pattern entirely opposite to that displayed by wild-type controls. Despite these major differences in T cell reactivity, B7-1/2-/- mice had only a limited reduction of granuloma size and fibrosis, without appreciable difference in cellular composition. These results show that substantial granuloma formation can occur under conditions of limited T cell expansion and restricted Th1-type cytokine production. They also support the notion that the combined effect of B7 signaling is not as critical for Th1 cell activation as it is for the development of the Th2 dominant environment characteristic of the evolving schistosome infection in H-2b mice.  (+info)

Recombinant soluble form of PSGL-1 accelerates thrombolysis and prevents reocclusion in a porcine model. (5/1300)

BACKGROUND: We investigated whether administration of a soluble recombinant P-selectin glycoprotein ligand-1 chimera (rPSGL-Ig) in conjunction with thrombolytic therapy would enhance thrombolysis by preventing ongoing interactions of leukocytes with platelets and the injured arterial wall. METHODS AND RESULTS: An occlusive thrombus was formed in an internal iliac artery of Yorkshire pigs by placement of a copper coil in the artery under fluoroscopic guidance. Pigs then received heparin and, 15 minutes later, either vehicle or rPSGL-Ig followed by infusion with 25 mg tissue plasminogen activator according to the 90-minute regimen. Blood flow through the artery was monitored by angiography and scored on a scale of 0 to 3. Lysis of the thrombus was accelerated by 70% in pigs treated with rPSGL-Ig 250 microg/kg compared with control (13.3+/-5.0 versus 44. 4+/-13.3 minutes; n=9 each). Eight of 9 control pigs reoccluded in 13.8+/-16.9 minutes after the end of tissue plasminogen activator infusion, whereas no reocclusion was observed in 8 of 9 pigs in the rPSGL-Ig group. When the dose of rPSGL-Ig was increased to 500 microg/kg, time to lysis was shortened by 61% from control (18.0+/-8. 4 versus 46.0+/-8.9 minutes). Reocclusion occurred in 6.0+/-15.2 minutes in control but not in any rPSGL-Ig-treated pig (n=5 each). In addition, near-normal flow (score 2 or 3) after thrombolysis was achieved 59% and 58% faster in the 2 rPSGL-Ig groups than in their respective controls. CONCLUSIONS: Inhibition of leukocyte accumulation at the site of thrombosis with rPSGL-Ig may represent a safe therapeutic intervention that could be important in accelerating thrombolysis, achieving optimal reperfusion, and reducing incidence of acute reocclusion.  (+info)

Prevention of autoimmune recurrence and rejection by adenovirus-mediated CTLA4Ig gene transfer to the pancreatic graft in BB rat. (6/1300)

Type 1 diabetes is the result of a selective destruction of pancreatic islets by autoreactive T-cells. Therefore, in the context of islet or pancreas transplantation, newly transplanted beta-cells are threatened by both recurrent autoimmune and alloimmune responses in recipients with type 1 diabetes. In the present study, using spontaneously diabetic BB rats, we demonstrate that whereas isolated islets are susceptible to autoimmune recurrence and rejection, pancreaticoduodenal grafts are resistant to these biological processes. This resistance is mediated by lymphohematopoietic cells transplanted with the graft, since inactivation of these passenger cells by irradiation uniformly rendered the pancreaticoduodenal grafts susceptible to recurrent autoimmunity. We further studied the impact of local immunomodulation on autoimmune recurrence and rejection by ex vivo adenovirus-mediated CTLA4Ig gene transfer to pancreaticoduodenal grafts. Syngeneic DR-BB pancreaticoduodenal grafts transduced with AdmCTLA4Ig were rescued from recurrent autoimmunity. In fully histoincompatible LEW-->BB transplants, in which rejection and recurrence should be able to act synergistically, AdmCTLA4Ig transduced LEW-pancreaticoduodenal allografts enjoyed markedly prolonged survival in diabetic BB recipients. In situ reverse transcription-polymerase chain reaction revealed that transferred CTLA4Ig gene was strongly expressed in both endocrine and exocrine tissues on day 3. These results indicate the potential utility of local CD28-B7 costimulatory blockade for prevention of alloimmune and autoimmune destruction of pancreatic grafts in type 1 diabetic hosts.  (+info)

Phenotypic analysis of lymphocytes and monocytes/macrophages in peripheral blood and bronchoalveolar lavage fluid from patients with pulmonary sarcoidosis. (7/1300)

BACKGROUND: The granulomatous inflammation in sarcoidosis is driven by the interplay between T cells and macrophages. To gain a better understanding of this process the expression by these cells of cell surface activation markers, co-stimulatory molecules, and adhesion molecules was analysed. METHODS: CD4+ and CD8+ T lymphocytes from peripheral blood (PBL) or bronchoalveolar lavage (BAL) fluid, as well as paired peripheral blood monocytes and alveolar macrophages from 27 patients with sarcoidosis were analysed by flow cytometry. RESULTS: CD26, CD54, CD69, CD95, and gp240 were all overexpressed in T cells from BAL fluid compared with those from PBL in both the CD4+ and CD8+ subsets, while CD57 was overexpressed only in BAL CD4+ cells. In contrast, CD28 tended to be underexpressed in the BAL T cells. Monocyte/macrophage markers included CD11a, CD11b, CD11c, CD14, CD16, CD54, CD71, CD80 and CD86 and HLA class II. CD11a expression in alveolar macrophages (and peripheral blood monocytes) was increased in patients with active disease and correlated positively with the percentage of BAL lymphocytes. Expression of CD80 in macrophages correlated with the BAL CD4/CD8 ratio. CONCLUSIONS: Our data indicate substantial activation of both CD4+ and CD8+ lung T cells in sarcoidosis. There were also increased numbers of BAL lymphocytes whose phenotypic characteristics have earlier been associated with clonally expanded, replicatively senescent cells of the Th1 type.  (+info)

The role of CTLA-4 in the regulation of T cell immune responses. (8/1300)

Over the past few years a great deal of research has examined how T cell-dependent immune responses are initiated and subsequently regulated. Ligation of the TCR with an antigenic peptide bound to an MHC protein on a professional APC provides the crucial antigen-specific stimulus required for T cell activation. Interaction of CD28 with CD80 or CD86 molecules on APC initiates a costimulatory or second signal within the T cell which augments and sustains T cell activation initiated through the TCR. However, recently it has become clear that T cell immune responses are a result of a balance between stimulatory and inhibitory signals. Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) is a cell surface molecule that is expressed nearly exclusively on CD4+ and CD8+ T cells. Investigation into the role of CTLA-4 in the regulation of T cell immune responses has revealed that CTLA-4 is a very important molecule involved in the maintenance of T cell homeostasis. In the present review, evidence for the proposed inhibitory role of CTLA-4 is examined and a model suggesting a role for CTLA-4 in both early and late stages of T cell activation is presented.  (+info)

Immunoconjugates are biomolecules created by the conjugation (coupling) of an antibody or antibody fragment with a cytotoxic agent, such as a drug, radionuclide, or toxin. This coupling is designed to direct the cytotoxic agent specifically to target cells, usually cancer cells, against which the antibody is directed, thereby increasing the effectiveness and reducing the side effects of the therapy.

The antibody part of the immunoconjugate recognizes and binds to specific antigens (proteins or other molecules) on the surface of the target cells, while the cytotoxic agent part enters the cell and disrupts its function, leading to cell death. The linker between the two parts is designed to be stable in circulation but can release the cytotoxic agent once inside the target cell.

Immunoconjugates are a promising area of research in targeted cancer therapy, as they offer the potential for more precise and less toxic treatments compared to traditional chemotherapy. However, their development and use also pose challenges, such as ensuring that the immunoconjugate binds specifically to the target cells and not to normal cells, optimizing the dose and schedule of treatment, and minimizing the risk of resistance to the therapy.

Immunotoxins are biomolecules that combine the specificity of an antibody with the toxicity of a toxin. They are created by chemically linking a monoclonal antibody (that recognizes and binds to a specific cell surface antigen) to a protein toxin (that inhibits protein synthesis in cells). The immunotoxin selectively binds to the target cell, gets internalized, and releases the toxin into the cytosol, leading to cell death. Immunotoxins have been explored as potential therapeutic agents for targeted cancer therapy and treatment of other diseases.

Maytansine is not typically defined in a medical dictionary as it is not a medical term itself, but rather a chemical compound. Maytansine is a natural product that was initially isolated from the bark of the African shrub Maytenus ovatus. It is a potent antimitotic agent, which means it interferes with cell division and has been studied for its potential use in cancer treatment.

In medical contexts, maytansine is often discussed in relation to specific drugs or therapies that utilize this compound. For example, the drug DM1 (also known as maytansinoid 1) is a derivative of maytansine and has been conjugated with monoclonal antibodies for targeted cancer therapy.

Therefore, when discussing 'Maytansine' in a medical context, it generally refers to the chemical compound or its derivatives that have potential use as anticancer agents.

Immunoproteins, also known as antibodies or immunoglobulins, are proteins produced by the immune system in response to the presence of foreign substances such as bacteria, viruses, and toxins. These Y-shaped proteins recognize, bind to, and help neutralize or remove harmful antigens from the body.

There are five classes of immunoproteins (IgA, IgD, IgE, IgG, and IgM) that differ in their structure, function, and location in the body. For example, IgA is found in tears, saliva, and breast milk and helps protect mucous membranes from pathogens, while IgG is the most abundant antibody in the blood and provides long-term immunity to previously encountered antigens.

Overall, immunoproteins play a critical role in the body's defense mechanisms against infection and disease.

Heterocyclic compounds are organic molecules that contain a ring structure made up of at least one atom that is not carbon, known as a heteroatom. These heteroatoms can include nitrogen, oxygen, sulfur, or other elements. In the case of "1-ring" heterocyclic compounds, the molecule contains a single ring structure composed of these heteroatoms and carbon atoms. Examples of 1-ring heterocyclic compounds include pyridine (contains one nitrogen atom in the ring), furan (contains one oxygen atom in the ring), and thiophene (contains one sulfur atom in the ring). These compounds play important roles in various biological processes and are also found in many drugs, dyes, and materials.

Yttrium radioisotopes are radioactive isotopes or variants of the element Yttrium, which is a rare earth metal. These radioisotopes are artificially produced and have unstable nuclei that emit radiation in the form of gamma rays or high-speed particles. Examples of yttrium radioisotopes include Yttrium-90 and Yttrium-86, which are used in medical applications such as radiotherapy for cancer treatment and molecular imaging for diagnostic purposes.

Yttrium-90 is a pure beta emitter with a half-life of 64.1 hours, making it useful for targeted radionuclide therapy. It can be used to treat liver tumors, leukemia, and lymphoma by attaching it to monoclonal antibodies or other targeting agents that selectively bind to cancer cells.

Yttrium-86 is a positron emitter with a half-life of 14.7 hours, making it useful for positron emission tomography (PET) imaging. It can be used to label radiopharmaceuticals and track their distribution in the body, providing information on the location and extent of disease.

It is important to note that handling and use of radioisotopes require specialized training and equipment due to their potential radiation hazards.

Radioimmunotherapy (RIT) is a medical treatment that combines the specificity of antibodies and the therapeutic effects of radiation to target and destroy cancer cells. It involves the use of radioactive isotopes, which are attached to monoclonal antibodies, that recognize and bind to antigens expressed on the surface of cancer cells. Once bound, the radioactivity emitted from the isotope irradiates the cancer cells, causing damage to their DNA and leading to cell death. This targeted approach helps minimize radiation exposure to healthy tissues and reduces side effects compared to conventional radiotherapy techniques. RIT has been used in the treatment of various hematological malignancies, such as non-Hodgkin lymphoma, and is being investigated for solid tumors as well.

Monoclonal antibodies are a type of antibody that are identical because they are produced by a single clone of cells. They are laboratory-produced molecules that act like human antibodies in the immune system. They can be designed to attach to specific proteins found on the surface of cancer cells, making them useful for targeting and treating cancer. Monoclonal antibodies can also be used as a therapy for other diseases, such as autoimmune disorders and inflammatory conditions.

Monoclonal antibodies are produced by fusing a single type of immune cell, called a B cell, with a tumor cell to create a hybrid cell, or hybridoma. This hybrid cell is then able to replicate indefinitely, producing a large number of identical copies of the original antibody. These antibodies can be further modified and engineered to enhance their ability to bind to specific targets, increase their stability, and improve their effectiveness as therapeutic agents.

Monoclonal antibodies have several mechanisms of action in cancer therapy. They can directly kill cancer cells by binding to them and triggering an immune response. They can also block the signals that promote cancer growth and survival. Additionally, monoclonal antibodies can be used to deliver drugs or radiation directly to cancer cells, increasing the effectiveness of these treatments while minimizing their side effects on healthy tissues.

Monoclonal antibodies have become an important tool in modern medicine, with several approved for use in cancer therapy and other diseases. They are continuing to be studied and developed as a promising approach to treating a wide range of medical conditions.

Ricin is defined as a highly toxic protein that is derived from the seeds of the castor oil plant (Ricinus communis). It can be produced as a white, powdery substance or a mistable aerosol. Ricin works by getting inside cells and preventing them from making the proteins they need. Without protein, cells die. Eventually, this can cause organ failure and death.

It is not easily inhaled or absorbed through the skin, but if ingested or injected, it can be lethal in very small amounts. There is no antidote for ricin poisoning - treatment consists of supportive care. Ricin has been used as a bioterrorism agent in the past and continues to be a concern due to its relative ease of production and potential high toxicity.

Copper radioisotopes are radioactive isotopes or variants of the chemical element copper. These isotopes have an unstable nucleus and emit radiation as they decay over time. Copper has several radioisotopes, including copper-64, copper-67, and copper-60, among others. These radioisotopes are used in various medical applications such as diagnostic imaging, therapy, and research. For example, copper-64 is used in positron emission tomography (PET) scans to help diagnose diseases like cancer, while copper-67 is used in targeted radionuclide therapy for cancer treatment. The use of radioisotopes in medicine requires careful handling and regulation due to their radiation hazards.

Heterocyclic compounds are organic compounds that contain at least one atom within the ring structure, other than carbon, such as nitrogen, oxygen, sulfur or phosphorus. These compounds make up a large class of naturally occurring and synthetic materials, including many drugs, pigments, vitamins, and antibiotics. The presence of the heteroatom in the ring can have significant effects on the physical and chemical properties of the compound, such as its reactivity, stability, and bonding characteristics. Examples of heterocyclic compounds include pyridine, pyrimidine, and furan.

Indium radioisotopes refer to specific types of radioactive indium atoms, which are unstable and emit radiation as they decay. Indium is a chemical element with the symbol In and atomic number 49. Its radioisotopes are often used in medical imaging and therapy due to their unique properties.

For instance, one commonly used indium radioisotope is Indium-111 (^111In), which has a half-life of approximately 2.8 days. It emits gamma rays, making it useful for diagnostic imaging techniques such as single-photon emission computed tomography (SPECT). In clinical applications, indium-111 is often attached to specific molecules or antibodies that target particular cells or tissues in the body, allowing medical professionals to monitor biological processes and identify diseases like cancer.

Another example is Indium-113m (^113mIn), which has a half-life of about 99 minutes. It emits low-energy gamma rays and is used as a source for in vivo counting, typically in the form of indium chloride (InCl3) solution. This radioisotope can be used to measure blood flow, ventilation, and other physiological parameters.

It's important to note that handling and using radioisotopes require proper training and safety measures due to their ionizing radiation properties.

Immunoglobulin fragments refer to the smaller protein units that are formed by the digestion or break-down of an intact immunoglobulin, also known as an antibody. Immunoglobulins are large Y-shaped proteins produced by the immune system to identify and neutralize foreign substances such as pathogens or toxins. They consist of two heavy chains and two light chains, held together by disulfide bonds.

The digestion or break-down of an immunoglobulin can occur through enzymatic cleavage, which results in the formation of distinct fragments. The most common immunoglobulin fragments are:

1. Fab (Fragment, antigen binding) fragments: These are formed by the digestion of an intact immunoglobulin using the enzyme papain. Each Fab fragment contains a single antigen-binding site, consisting of a portion of one heavy chain and one light chain. The Fab fragments retain their ability to bind to specific antigens.
2. Fc (Fragment, crystallizable) fragments: These are formed by the digestion of an intact immunoglobulin using the enzyme pepsin or through the natural breakdown process in the body. The Fc fragment contains the constant region of both heavy chains and is responsible for effector functions such as complement activation, binding to Fc receptors on immune cells, and antibody-dependent cellular cytotoxicity (ADCC).

These immunoglobulin fragments play crucial roles in various immune responses and diagnostic applications. For example, Fab fragments can be used in immunoassays for the detection of specific antigens, while Fc fragments can mediate effector functions that help eliminate pathogens or damaged cells from the body.

Heterologous transplantation is a type of transplantation where an organ or tissue is transferred from one species to another. This is in contrast to allogeneic transplantation, where the donor and recipient are of the same species, or autologous transplantation, where the donor and recipient are the same individual.

In heterologous transplantation, the immune systems of the donor and recipient are significantly different, which can lead to a strong immune response against the transplanted organ or tissue. This is known as a graft-versus-host disease (GVHD), where the immune cells in the transplanted tissue attack the recipient's body.

Heterologous transplantation is not commonly performed in clinical medicine due to the high risk of rejection and GVHD. However, it may be used in research settings to study the biology of transplantation and to develop new therapies for transplant rejection.

Tissue distribution, in the context of pharmacology and toxicology, refers to the way that a drug or xenobiotic (a chemical substance found within an organism that is not naturally produced by or expected to be present within that organism) is distributed throughout the body's tissues after administration. It describes how much of the drug or xenobiotic can be found in various tissues and organs, and is influenced by factors such as blood flow, lipid solubility, protein binding, and the permeability of cell membranes. Understanding tissue distribution is important for predicting the potential effects of a drug or toxin on different parts of the body, and for designing drugs with improved safety and efficacy profiles.

Immunotherapy is a type of medical treatment that uses the body's own immune system to fight against diseases, such as cancer. It involves the use of substances (like vaccines, medications, or immune cells) that stimulate or suppress the immune system to help it recognize and destroy harmful disease-causing cells or agents, like tumor cells.

Immunotherapy can work in several ways:

1. Activating the immune system: Certain immunotherapies boost the body's natural immune responses, helping them recognize and attack cancer cells more effectively.
2. Suppressing immune system inhibitors: Some immunotherapies target and block proteins or molecules that can suppress the immune response, allowing the immune system to work more efficiently against diseases.
3. Replacing or enhancing specific immune cells: Immunotherapy can also involve administering immune cells (like T-cells) that have been genetically engineered or modified to recognize and destroy cancer cells.

Immunotherapies have shown promising results in treating various types of cancer, autoimmune diseases, and allergies. However, they can also cause side effects, as an overactive immune system may attack healthy tissues and organs. Therefore, careful monitoring is necessary during immunotherapy treatment.

"Nude mice" is a term used in the field of laboratory research to describe a strain of mice that have been genetically engineered to lack a functional immune system. Specifically, nude mice lack a thymus gland and have a mutation in the FOXN1 gene, which results in a failure to develop a mature T-cell population. This means that they are unable to mount an effective immune response against foreign substances or organisms.

The name "nude" refers to the fact that these mice also have a lack of functional hair follicles, resulting in a hairless or partially hairless phenotype. This feature is actually a secondary consequence of the same genetic mutation that causes their immune deficiency.

Nude mice are commonly used in research because their weakened immune system makes them an ideal host for transplanted tumors, tissues, and cells from other species, including humans. This allows researchers to study the behavior of these foreign substances in a living organism without the complication of an immune response. However, it's important to note that because nude mice lack a functional immune system, they must be kept in sterile conditions and are more susceptible to infection than normal mice.

Neoplasm transplantation is not a recognized or established medical procedure in the field of oncology. The term "neoplasm" refers to an abnormal growth of cells, which can be benign or malignant (cancerous). "Transplantation" typically refers to the surgical transfer of living cells, tissues, or organs from one part of the body to another or between individuals.

The concept of neoplasm transplantation may imply the transfer of cancerous cells or tissues from a donor to a recipient, which is not a standard practice due to ethical considerations and the potential harm it could cause to the recipient. In some rare instances, researchers might use laboratory animals to study the transmission and growth of human cancer cells, but this is done for scientific research purposes only and under strict regulatory guidelines.

In summary, there is no medical definition for 'Neoplasm Transplantation' as it does not represent a standard or ethical medical practice.

Photosensitizing agents are substances that, when exposed to light, particularly ultraviolet or visible light, can cause chemical reactions leading to the production of reactive oxygen species. These reactive oxygen species can interact with biological tissues, leading to damage and a variety of phototoxic or photoallergic adverse effects.

Photosensitizing agents are used in various medical fields, including dermatology and oncology. In dermatology, they are often used in the treatment of conditions such as psoriasis and eczema, where a photosensitizer is applied to the skin and then activated with light to reduce inflammation and slow the growth of skin cells.

In oncology, photosensitizing agents are used in photodynamic therapy (PDT), a type of cancer treatment that involves administering a photosensitizer, allowing it to accumulate in cancer cells, and then exposing the area to light. The light activates the photosensitizer, which produces reactive oxygen species that damage the cancer cells, leading to their death.

Examples of photosensitizing agents include porphyrins, chlorophyll derivatives, and certain antibiotics such as tetracyclines and fluoroquinolones. It is important for healthcare providers to be aware of the potential for photosensitivity when prescribing these medications and to inform patients of the risks associated with exposure to light.

Immunoglobulin G (IgG) is a type of antibody, which is a protective protein produced by the immune system in response to foreign substances like bacteria or viruses. IgG is the most abundant type of antibody in human blood, making up about 75-80% of all antibodies. It is found in all body fluids and plays a crucial role in fighting infections caused by bacteria, viruses, and toxins.

IgG has several important functions:

1. Neutralization: IgG can bind to the surface of bacteria or viruses, preventing them from attaching to and infecting human cells.
2. Opsonization: IgG coats the surface of pathogens, making them more recognizable and easier for immune cells like neutrophils and macrophages to phagocytose (engulf and destroy) them.
3. Complement activation: IgG can activate the complement system, a group of proteins that work together to help eliminate pathogens from the body. Activation of the complement system leads to the formation of the membrane attack complex, which creates holes in the cell membranes of bacteria, leading to their lysis (destruction).
4. Antibody-dependent cellular cytotoxicity (ADCC): IgG can bind to immune cells like natural killer (NK) cells and trigger them to release substances that cause target cells (such as virus-infected or cancerous cells) to undergo apoptosis (programmed cell death).
5. Immune complex formation: IgG can form immune complexes with antigens, which can then be removed from the body through various mechanisms, such as phagocytosis by immune cells or excretion in urine.

IgG is a critical component of adaptive immunity and provides long-lasting protection against reinfection with many pathogens. It has four subclasses (IgG1, IgG2, IgG3, and IgG4) that differ in their structure, function, and distribution in the body.

'Tumor cells, cultured' refers to the process of removing cancerous cells from a tumor and growing them in controlled laboratory conditions. This is typically done by isolating the tumor cells from a patient's tissue sample, then placing them in a nutrient-rich environment that promotes their growth and multiplication.

The resulting cultured tumor cells can be used for various research purposes, including the study of cancer biology, drug development, and toxicity testing. They provide a valuable tool for researchers to better understand the behavior and characteristics of cancer cells outside of the human body, which can lead to the development of more effective cancer treatments.

It is important to note that cultured tumor cells may not always behave exactly the same way as they do in the human body, so findings from cell culture studies must be validated through further research, such as animal models or clinical trials.

Antibodies are proteins produced by the immune system in response to the presence of a foreign substance, such as a bacterium or virus. They are capable of identifying and binding to specific antigens (foreign substances) on the surface of these invaders, marking them for destruction by other immune cells. Antibodies are also known as immunoglobulins and come in several different types, including IgA, IgD, IgE, IgG, and IgM, each with a unique function in the immune response. They are composed of four polypeptide chains, two heavy chains and two light chains, that are held together by disulfide bonds. The variable regions of the heavy and light chains form the antigen-binding site, which is specific to a particular antigen.

Neoplasms are abnormal growths of cells or tissues in the body that serve no physiological function. They can be benign (non-cancerous) or malignant (cancerous). Benign neoplasms are typically slow growing and do not spread to other parts of the body, while malignant neoplasms are aggressive, invasive, and can metastasize to distant sites.

Neoplasms occur when there is a dysregulation in the normal process of cell division and differentiation, leading to uncontrolled growth and accumulation of cells. This can result from genetic mutations or other factors such as viral infections, environmental exposures, or hormonal imbalances.

Neoplasms can develop in any organ or tissue of the body and can cause various symptoms depending on their size, location, and type. Treatment options for neoplasms include surgery, radiation therapy, chemotherapy, immunotherapy, and targeted therapy, among others.

A cell line that is derived from tumor cells and has been adapted to grow in culture. These cell lines are often used in research to study the characteristics of cancer cells, including their growth patterns, genetic changes, and responses to various treatments. They can be established from many different types of tumors, such as carcinomas, sarcomas, and leukemias. Once established, these cell lines can be grown and maintained indefinitely in the laboratory, allowing researchers to conduct experiments and studies that would not be feasible using primary tumor cells. It is important to note that tumor cell lines may not always accurately represent the behavior of the original tumor, as they can undergo genetic changes during their time in culture.

Cell survival refers to the ability of a cell to continue living and functioning normally, despite being exposed to potentially harmful conditions or treatments. This can include exposure to toxins, radiation, chemotherapeutic drugs, or other stressors that can damage cells or interfere with their normal processes.

In scientific research, measures of cell survival are often used to evaluate the effectiveness of various therapies or treatments. For example, researchers may expose cells to a particular drug or treatment and then measure the percentage of cells that survive to assess its potential therapeutic value. Similarly, in toxicology studies, measures of cell survival can help to determine the safety of various chemicals or substances.

It's important to note that cell survival is not the same as cell proliferation, which refers to the ability of cells to divide and multiply. While some treatments may promote cell survival, they may also inhibit cell proliferation, making them useful for treating diseases such as cancer. Conversely, other treatments may be designed to specifically target and kill cancer cells, even if it means sacrificing some healthy cells in the process.

A cell line is a culture of cells that are grown in a laboratory for use in research. These cells are usually taken from a single cell or group of cells, and they are able to divide and grow continuously in the lab. Cell lines can come from many different sources, including animals, plants, and humans. They are often used in scientific research to study cellular processes, disease mechanisms, and to test new drugs or treatments. Some common types of human cell lines include HeLa cells (which come from a cancer patient named Henrietta Lacks), HEK293 cells (which come from embryonic kidney cells), and HUVEC cells (which come from umbilical vein endothelial cells). It is important to note that cell lines are not the same as primary cells, which are cells that are taken directly from a living organism and have not been grown in the lab.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

Immunoconjugates are antibodies conjugated (joined) to a second molecule, usually a toxin, radioisotope or label. These ... Arming antibodies: prospects and challenges for immunoconjugates. 2005 10 pages. v t e (Articles with short description, Short ... Technology Insight: cytotoxic drug immunoconjugates for cancer therapy. 2007 looks useful from the abstract. Targeted Therapy ... of Cancer: New Prospects for Antibodies and Immunoconjugates. 2006 full article, 18 pages. ...
Effective Immunoconjugate Therapy in Cancer Models Targeting a Serine Protease of Tumor Fibroblasts Elinborg Ostermann; ... Immunoconjugate mAb FAP5-DM1 is highly efficacious in cancer xenograft models. The in vivo efficacy of mAb FAP5-DM1 given once ... Immunoconjugates. The mAb FAP5-maytansinoid conjugates mAb FAP5-SPP-DM1 (here designated mAb FAP5-DM1), mAb FAP5-SPDB-DM4 (mAb ... Characterization and cross-reactivity of mAb FAP5 and mAb FAP5-maytansinoid immunoconjugates. A, selective binding of mAb FAP5 ...
However, T-DM1 is known to be a heterogeneous mixture of immunoconjugates, which compromises its therapeutic window. Moreover, ... Finally, the candidate will participate to the in vitro biological evaluation of the new immunoconjugates. ADCs ...
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"Drug Immunoconjugates". In Oldham, Robert K.; Dillman, Robert O. (eds.). Principles of Cancer Biotherapy (5th ed.). pp. 451-62 ...
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Immunoconjugates / pharmacology* * Macaca fascicularis * Maytansine / chemistry* * Mice * Mice, SCID * Neoplasms, Glandular and ...
Results: Pretreatment of mice with an antibody/IL-2 immunoconjugate resulted in an approximately fourfold increase in ... The cytokine activity of the immunoconjugates was determined by assaying their ability to promote the proliferation of a mouse ... and 3 days later they were subjected to biodistribution analysis to measure the ability of each immunoconjugate to enhance ...
Antibody, Immunoconjugates and Radiopharmaceuticals., , Henslee PJ, Gilinsky NH, Cibull ML, Thompson JS, Scannon PJ, Byers VS ...
Antibodies/immunoconjugates (1) * LIFESTYLE RISK FACTORS (23) * Diet (3) * Tobacco use (1) ...
... and good stability of the radioimmunoconjugate are essential features for a successful immunoconjugate for imaging or therapy. ... PREPARATION AND INTEGRITY EXAMINATION OF FREEZE DRIED KIT OF TRASTUZUMAB-IMMUNOCONJUGATES AND COLD LABELED IMMUNOCONJUGATES BY ... In this study, the radiolabeling efficiency, in vitro stability, and biodistribution of immunoconjugates with eight different ... Efficiencies of 64Cu radiolabeling were dependent on the concentration of immunoconjugate. Notably, the 64Cu-NOTA-rituximab ...
EphA2 immunoconjugate as molecularly targeted chemotherapy for ovarian carcinoma. J Natl Cancer Inst. 2009 Sep.101(17):1193- ...
If patient relapses, consider clinical trials evaluating novel agents (eg, bortezomib, lenalidomide, or immunoconjugates) or ...
TPMAL consists of a nanoliposome chemotherapy labeled with fluorophores for tracking and photosensitizer immunoconjugates for ...
Evaluation of anti-CD5 ricin A chain immunoconjugate for prevention of acute graft-vs.-host disease after HLA-identical marrow ...
Effective immunoconjugate therapy in cancer models targeting a serine protease of tumor fibroblasts. Clin Cancer Res. 2008;14: ... immunoconjugates (21), peptide-drug complexes bearing the consensus sequence for the enzymatic activity (22,23), vaccines (14, ...
... sandwich-type immunoconjugates were prepared by interaction with the respective Envision™-NP-secondary antibody. A microcell ... the tags were captured on the immunoconjugates and silver deposition was induced. This method provided LOD values of 0.024 pg· ... the corresponding hybrids were prepared and used to form immunoconjugates with anti-CEA, anti-PSA and anti-AFP secondary ... have been used as carrier tags and redox mediators to prepare immunoconjugates for distinguishable detection in various ...
J. W. Lee, H. D. Han, M. M. K. Shahzad et al., "EphA2 immunoconjugate as molecularly targeted chemotherapy for ovarian ...
My doctoral programme investigates the immune cells that infiltrate tumours (TILs) which are the basis of immunotherapy, a relatively new set of very powerful cancer treatments. Immunotherapy could allow better cancer treatment by exploiting the ability of certain immune cells to identify and eliminate undesirable cells such as cancer cells. I aim to provide new insights into the genetic traits of the tumour-infiltrating cells to look for potential new druggable targets using Illumina and Oxford Nanopore sequencing technology. In addition, I am generating organoids from pancreatic cancer mouse models for co-culture with autologous peripheral blood lymphocytes. The goal is to isolate any reactive T cells from the pancreatic organoid-lymphocyte co-culture and to perform RNA sequencing - bulk and single cell - of the tumour-infiltrating lymphocytes. ...
Fc and albumin fusions as well as immunoconjugates prior to in vivo studies. ...
If patient relapses, consider clinical trials evaluating novel agents (eg, bortezomib, lenalidomide, or immunoconjugates) or ...
This study can be performed in vitro (reactivity of the antibody or immunoconjugate should be determined with a quick-frozen ...
... and immunoconjugates in certain forms of breast cancer (covered in Part II) and in Hodgkin lymphoma represent just the ... Treatment of this cancer is also relying on immune-stimulation and bone-seeking radio-immunoconjugates-with all of these ...
... and immunoconjugate was detected with enhanced chemiluminescence. The membrane was then incubated with stripping buffer (100 ...
Bratulic, S., Limeta, A., Dabestani, S., Birgisson, H., Enblad, G., Stålberg, K., Hesselager, G., Häggman, M., Höglund, M., Simonson, O. E., Stålberg, P., Lindman, H., Bång-Rudenstam, A., Ekstrand, M., Kumar, G., Cavarretta, I., Alfano, M., Pellegrino, F., Mandel-Clausen, T., Salanti, A., & 16 othersMaccari, F., Galeotti, F., Volpi, N., Daugaard, M., Belting, M., Lundstam, S., Stierner, U., Nyman, J., Bergman, B., Edqvist, P. H., Levin, M., Salonia, A., Kjölhede, H., Jonasch, E., Nielsen, J. & Gatto, F., 2022 Dec, In: Proceedings of the National Academy of Sciences of the United States of America. 119, 50, e2115328119.. Research output: Contribution to journal › Article › peer-review ...
... a phase I study of an anti-CD33 calicheamicin immunoconjugate. Blood. 1999;93:3678-3684. ...
... of pharmacologically active dexamethasone into activated endothelial cells by dexamethasone-anti-E-selectin immunoconjugate," ...
... immunoconjugates, antifolates, monoclonal antibodies, immunomodulatory agents, nucleoside analogs, proteasome inhibitors, ... Immunoconjugates. Fusion proteins have been engineered to achieve the following: act as decoy receptors; increase the ... Brentuximab vedotin (BV) is an immunoconjugate that combines an antitubulin agent with a CD30-specific chimeric monoclonal ... Recent research has led to the development of numerous agents, including HDACi, immunoconjugates, antifolates, monoclonal ...

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