Radioimmunotherapy

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Radioimmunotherapy
Radioimmunotherapy schematic.png
Schematic of radioimmunotherapy (RIT)
Other namesRIT
ICD-9-CM 92.28
MeSH D016499

Radioimmunotherapy (RIT) or Targeted radionuclide therapy (TRT) uses an antibody labeled with a radionuclide to deliver cytotoxic radiation to a target cell. [1] It is a form of unsealed source radiotherapy. In cancer therapy, an antibody with specificity for a tumor-associated antigen is used to deliver a lethal dose of radiation to the tumor cells. The ability for the antibody to specifically bind to a tumor-associated antigen increases the dose delivered to the tumor cells while decreasing the dose to normal tissues. By its nature, RIT requires a tumor cell to express an antigen that is unique to the neoplasm or is not accessible in normal cells.

Contents

History of available agents

NameDescription FDA status EMA status
Ibritumomab tiuxetan (Zevalin) monoclonal antibody anti-CD20 conjugated to a molecule that chelates Yttrium-90.Approved (2002) [2] [3] Authorised (2004) [4]
Iodine (131I) tositumomab (Bexxar)links a molecule containing Iodine-131 to an anti-CD20 monoclonal antibodyApproved (2003) [5]
Withdrawn (2014) [6]
Orphan drug (2003)
Withdrawn (2015) [7]
Lutetium (177Lu) lilotomab satetraxetan (Betalutin)combination of lutetium-177 and an anti-CD37 monoclonal antibody Fast track (2020) [8] Orphan drug (2020) [9]

131I tositumomab and 90Y ibritumomab tiuxetan were the first agents of radioimmunotherapy, and they were approved for the treatment of refractory non-Hodgkin's lymphoma. This means they are used in patients whose lymphoma is refractory to conventional chemotherapy and the monoclonal antibody rituximab.

Agents in clinical development

A set of radioimmunotherapy drugs that rely upon an alpha-emitting isotope (e.g., bismuth-213 or, preferably, actinium-225), rather than a beta emitter, as the killing source of radiation is being developed. Several phase II clinical trials for the treatment of acute myeloid leukemia have been carried out using alpha-emitting RITs. [10] [11]

90Y-FF-21101 is a monoclonal antibody against P-cadherin radiolabeled with yttrium-90. [12] It is one of several RIT treatments under investigation intending to treat solid tumors. [13] A phase I clinical trial began in 2015. [14]

Other applications (non-approved indications)

Other types of cancer for which RIT has therapeutic potential include prostate cancer, [15] metastatic melanoma, [16] ovarian cancer, [17] neoplastic meningitis, [17] leukemia, [18] high-grade brain glioma, [19] and metastatic colorectal cancer. [20]

Components of the extracellular matrix and the tumor microenvironment can also be targeted by radioimmunotherapy, such as Netrin-1 [21] (an axon guidance protein) and FAP (a marker for cancer associated fibroblasts). [22]

Related Research Articles

This is a list of terms related to oncology. The original source for this list was the US National Cancer Institute's public domain Dictionary of Cancer Terms.

<sup>90</sup>Y-DOTA-biotin

90Y-DOTA-biotin consists of a radioactive substance (yttrium-90) complexed by a chelating agent (DOTA), which in turn is attached to the vitamin biotin via a chemical linker. It is used experimentally in pretargeted radioimmunotherapy. Animal studies have been conducted as well as clinical studies in humans.

<span class="mw-page-title-main">Cancer immunotherapy</span> Artificial stimulation of the immune system to treat cancer

Cancer immunotherapy is the stimulation of the immune system to treat cancer, improving on the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology and a growing subspecialty of oncology.

<span class="mw-page-title-main">Ibritumomab tiuxetan</span> Radioimmunotherapy treatment

Ibritumomab tiuxetan, sold under the trade name Zevalin, is a monoclonal antibody radioimmunotherapy treatment for non-Hodgkin's lymphoma. The drug uses the monoclonal mouse IgG1 antibody ibritumomab in conjunction with the chelator tiuxetan, to which a radioactive isotope is added. Tiuxetan is a modified version of DTPA whose carbon backbone contains an isothiocyanatobenzyl and a methyl group.

<span class="mw-page-title-main">Targeted therapy</span> Type of therapy

Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer, others being hormonal therapy and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth, rather than by simply interfering with all rapidly dividing cells. Because most agents for targeted therapy are biopharmaceuticals, the term biologic therapy is sometimes synonymous with targeted therapy when used in the context of cancer therapy. However, the modalities can be combined; antibody-drug conjugates combine biologic and cytotoxic mechanisms into one targeted therapy.

Tositumomab is a murine monoclonal antibody which targets the CD20 antigen produced in mammalian cell. It was combined with iodine-131 to produce a radiopharmaceutical for unsealed source radiotherapy, Iodine-131 Tositumomab, for the treatment of non-Hodgkins lymphoma. It is classified as a IgG2a lambda antibody.

<span class="mw-page-title-main">Monoclonal antibody therapy</span> Form of immunotherapy

Monoclonal antibody therapy is a form of immunotherapy that uses monoclonal antibodies (mAbs) to bind monospecifically to certain cells or proteins. The objective is that this treatment will stimulate the patient's immune system to attack those cells. Alternatively, in radioimmunotherapy a radioactive dose localizes a target cell line, delivering lethal chemical doses. Antibodies are used to bind to molecules involved in T-cell regulation to remove inhibitory pathways that block T-cell responses. This is known as immune checkpoint therapy.

Epratuzumab is a humanized monoclonal antibody. Potential uses may be found in oncology and in treatment of inflammatory autoimmune disorders, such as systemic lupus erythematosus (SLE).

Mapatumumab (HGS-ETR1) is an experimental human monoclonal antibody undergoing clinical trials for the treatment of cancer. It targets TRAIL-R1, also known as DR4, which is expressed on the surface of many tumor cell types.

Chemoimmunotherapy is chemotherapy combined with immunotherapy. Chemotherapy uses different drugs to kill or slow the growth of cancer cells; immunotherapy uses treatments to stimulate or restore the ability of the immune system to fight cancer. A common chemoimmunotherapy regimen is CHOP combined with rituximab (CHOP-R) for B-cell non-Hodgkin lymphomas.

Nuclear medicine physicians, also called nuclear radiologists or simply nucleologists, are medical specialists that use tracers, usually radiopharmaceuticals, for diagnosis and therapy. Nuclear medicine procedures are the major clinical applications of molecular imaging and molecular therapy. In the United States, nuclear medicine physicians are certified by the American Board of Nuclear Medicine and the American Osteopathic Board of Nuclear Medicine.

<span class="mw-page-title-main">Alpha particle</span> Helium-4 nucleus; particle of two protons and two neutrons

Alpha particles, also called alpha rays or alpha radiation, consist of two protons and two neutrons bound together into a particle identical to a helium-4 nucleus. They are generally produced in the process of alpha decay, but may also be produced in other ways. Alpha particles are named after the first letter in the Greek alphabet, α. The symbol for the alpha particle is α or α2+. Because they are identical to helium nuclei, they are also sometimes written as He2+
or 4
2
He2+
indicating a helium ion with a +2 charge. Once the ion gains electrons from its environment, the alpha particle becomes a normal helium atom 4
2
He
.

<span class="mw-page-title-main">Monomethyl auristatin E</span> Chemical compound

Monomethyl auristatin E (MMAE) is a synthetic antineoplastic agent. Because of its toxicity, it cannot be used as a drug itself; instead, it is linked to a monoclonal antibody (MAB) which directs it to the cancer cells. In International Nonproprietary Names for MMAE-MAB-conjugates, the name vedotin refers to MMAE plus its linking structure to the antibody. It is a potent antimitotic drug derived from peptides occurring in marine shell-less mollusc Dolabella auricularia called dolastatins which show potent activity in preclinical studies, both in vitro and in vivo, against a range of lymphomas, leukemia and solid tumors. These drugs show potency of up to 200 times that of vinblastine, another antimitotic drug used for Hodgkin lymphoma as well as other types of cancer.

<span class="mw-page-title-main">Antibody-drug conjugate</span> Class of biopharmaceutical drugs

Antibody-drug conjugates or ADCs are a class of biopharmaceutical drugs designed as a targeted therapy for treating cancer. Unlike chemotherapy, ADCs are intended to target and kill tumor cells while sparing healthy cells. As of 2019, some 56 pharmaceutical companies were developing ADCs.

Gene expression profiling has revealed that diffuse large B-cell lymphoma (DLBCL) is composed of at least 3 different sub-groups, each having distinct oncogenic mechanisms that respond to therapies in different ways. Germinal Center B-Cell like (GCB) DLBCLs appear to arise from normal germinal center B cells, while Activated B-cell like (ABC) DLBCLs are thought to arise from postgerminal center B cells that are arrested during plasmacytic differentiation. The differences in gene expression between GCB DLBCL and ABC DLBCL are as vast as the differences between distinct types of leukemia, but these conditions have historically been grouped together and treated as the same disease.

Targeted alpha-particle therapy is an in-development method of targeted radionuclide therapy of various cancers. It employs radioactive substances which undergo alpha decay to treat diseased tissue at close proximity. It has the potential to provide highly targeted treatment, especially to microscopic tumour cells. Targets include leukemias, lymphomas, gliomas, melanoma, and peritoneal carcinomatosis. As in diagnostic nuclear medicine, appropriate radionuclides can be chemically bound to a targeting biomolecule which carries the combined radiopharmaceutical to a specific treatment point.

Camidanlumab tesirine is an antibody-drug conjugate (ADC) composed of a human antibody that binds to the protein CD25, conjugated to a pyrrolobenzodiazepine dimer toxin. The experimental drug, developed by ADC Therapeutics is being tested in clinical trials for the treatment of B-cell Hodgkin's lymphoma (HL) and non-Hodgkin lymphoma (NHL), and for the treatment of B-cell acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).

<span class="mw-page-title-main">Peptide receptor radionuclide therapy</span> Type of radiotherapy

Peptide receptor radionuclide therapy (PRRT) is a type of radionuclide therapy, using a radiopharmaceutical that targets peptide receptors to deliver localised treatment, typically for neuroendocrine tumours (NETs).

<span class="mw-page-title-main">Pretargeting (imaging)</span>

Pretargeting (imaging) is a tool for nuclear medicine and radiotherapy. Imaging studies require a high contrast of target to background. This can be provided by using a biomarker which has a high affinity and specificity for its target.

<span class="mw-page-title-main">Thomas A. Waldmann</span> American immunologist (1930–2021)

Thomas A. Waldmann was an American immunologist who has worked on therapeutic monoclonal antibodies to the IL-2 receptor, Interleukin 15 (IL-15), and Adult T-cell Leukemia (ATL). Until the week he died, he was an active distinguished investigator at the Lymphoid Malignancies Branch of the National Cancer Institute.

References

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