Radioimmunotherapy
Medical intervention
From Wikipedia, the free encyclopedia
Radioimmunotherapy (RIT) 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.
History of available agents
| Name | Description | 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tositumomab (Bexxar) | links a molecule containing Iodine-131 to an anti-CD20 monoclonal antibody | Approved (2003)[5] Withdrawn (2014)[6] | Orphan drug (2003) Withdrawn (2015)[7] |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]