Radioimmunotherapy Explained

Radioimmunotherapy
Synonyms:RIT

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Withdrawn (2014)[6] 		Orphan drug (2003)
Withdrawn (2015)[7] 		- Lutetium (177Lu) lilotomab satetraxetan (Betalutin) combination of lutetium-177 and an anti-CD37 monoclonal antibody Fast track (2020)[8] Orphan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, 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]

External links

Notes and References

  1. Milenic . Diane E. . Brady . Erik D. . Brechbiel . Martin W. . Antibody-targeted radiation cancer therapy . Nature Reviews Drug Discovery . June 2004 . 3 . 6 . 488–499 . 10.1038/nrd1413 . 15173838. 22166498 .
  2. https://www.fda.gov/ohrms/DOCKETS/ac/01/slides/3782s2_02_idec/index.htm FIbritumomab Tiuxetan (Zevalin™) Radioimmunotherapy of Non-Hodgkin’s Lymphoma
  3. Rao AV, Akabani G, Rizzieri DA. Radioimmunotherapy for Non-Hodgkin's Lymphoma. Clin Med Res. 2005 Aug;3(3):157-65.
  4. Web site: Zevalin . European Medicines Agency . 8 November 2020.
  5. http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2003/tosicor062703L.htm Tositumomab and Iodine I 131 Tositumomab – Product Approval Information – Licensing Action
  6. Web site: Why Good Drugs Sometimes Fail: The Bexxar Story. 2013-08-26.
  7. Web site: EU/3/03/136 . European Medicines Agency . 8 November 2020.
  8. News: FDA grants fast track status to Betalutin for marginal zone lymphoma . Healio . 29 June 2020.
  9. Web site: EU/3/20/2280 . European Medicines Agency . 8 November 2020.
  10. Bodet-Milin . Caroline . Kraeber-Bodéré . Françoise . Eugène . Thomas . Guérard . François . Gaschet . Joëlle . Bailly . Clément . Mougin . Marie . Bourgeois . Mickaël . Faivre-Chauvet . Alain . Chérel . Michel . Chevallier . Patrice . Radioimmunotherapy for Treatment of Acute Leukemia . Seminars in Nuclear Medicine . March 2016 . 46 . 2 . 135–146 . 10.1053/j.semnuclmed.2015.10.007 . 26897718.
  11. Pandit-Taskar . Neeta . Targeted Radioimmunotherapy and Theranostics with Alpha Emitters . Journal of Medical Imaging and Radiation Sciences . December 2019 . 50 . 4 . S41–S44 . 10.1016/j.jmir.2019.07.006 . 31451417 . free .
  12. Subbiah . Vivek . Erwin . William . Mawlawi . Osama . McCoy . Asa . Wages . David . Wheeler . Catherine . Gonzalez-Lepera . Carlos . Liu . Holly . Macapinlac . Homer . Meric-Bernstam . Funda . Hong . David S. . Pant . Shubham . Le . Dao . Santos . Elmer . Gonzalez . Jose . Roszik . Jason . Suzuki . Takeaki . Subach . Ruth Ann . Madden . Timothy . Johansen . Mary . Nomura . Fumiko . Satoh . Hirokazu . Matsuura . Tadashi . Kajita . Masamichi . Nakamura . Eri . Funase . Yuichi . Matsushima . Satoshi . Ravizzini . Gregory . Phase I Study of P-cadherin–targeted Radioimmunotherapy with 90 Y-FF-21101 Monoclonal Antibody in Solid Tumors . Clinical Cancer Research . 18 August 2020 . 26 . 22 . 1078–0432.CCR–20-0037 . 10.1158/1078-0432.CCR-20-0037 . 32816889. free .
  13. Zaheer . Javeria . Kim . Hyeongi . Lee . Yong-Jin . Kim . Jin Su . Lim . Sang Moo . Combination Radioimmunotherapy Strategies for Solid Tumors . International Journal of Molecular Sciences . 8 November 2019 . 20 . 22 . 5579 . 10.3390/ijms20225579 . 31717302 . 6888084. free .
  14. https://clinicaltrials.gov/ct2/show/NCT02454010 A Phase 1 Dose-escalation Study of Radio- Labeled Antibody, FF-21101(90Y) for the Treatment of Advanced Cancer
  15. Smith-Jones PM. Radioimmunotherapy of prostate cancer. Q J Nucl Med Mol Imaging. 2004 Dec;48(4):297-304.
  16. Dadachova E, Nosanchuk JD, Shi L, Schweitzer AD, Frenkel A, Nosanchuk JS, and Casadevall A. Dead cells in melanoma tumors provide abundant antigen for targeted delivery of ionizing radiation by a monoclonal antibody to melanin. Proc Natl Acad Sci USA 2004;101: 14865-70.
  17. Zalutsky MR, Pozzi OR. Radioimmunotherapy with alpha-particle emitting radionuclides. Q J Nucl Med Mol Imaging. 2004 Dec;48(4):289-96.
  18. Burke JM, Jurcic JG. Radioimmunotherapy of leukemia. Adv Pharmacol. 2004;51:185-208.
  19. Quang TS, Brady LW. Radioimmunotherapy as a novel treatment regimen: 125I-labeled monoclonal antibody 425 in the treatment of high-grade brain gliomas. Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):972-5.
  20. Wong JY, Shibata S, Williams LE, Kwok CS, Liu A, Chu DZ, Yamauchi DM, Wilczynski S, Ikle DN, Wu AM, Yazaki PJ, Shively JE, Doroshow JH, Raubitschek AA. A Phase I trial of 90Y-anti-carcinoembryonic antigen chimeric T84.66 radioimmunotherapy with 5-fluorouracil in patients with metastatic colorectal cancer. Clin Cancer Res. 2003 Dec 1;9(16 Pt 1):5842-52
  21. Kryza D, Wischhusen J, Richaud M, Hervieu M, Sidi Boumedine J, Delcros JG, Besse S, Baudier T, Laval PA, Breusa S, Boutault E, Clermidy H, Rama N, Ducarouge B, Devouassoux-Shisheboran M, Chezal JM, Giraudet AL, Walter T, Mehlen P, Sarrut D, Gibert B.From netrin-1-targeted SPECT/CT to internal radiotherapy for management of advanced solid tumors. EMBO Mol Med. 2023 Apr 11;15(4):e16732. doi: 10.15252/emmm.202216732. Epub 2023 Mar 6. PMID: 36876343
  22. Marko Magdi Abdou Sidrak, Maria Silvia De Feo, Ferdinando Corica, Joana Gorica, Miriam Conte, Luca Filippi, Orazio Schillaci, Giuseppe De Vincentis, and Viviana Frantellizzi1,Fibroblast Activation Protein Inhibitor (FAPI)-Based Theranostics—Where We Are at and Where We Are Heading: A Systematic Review Int J Mol Sci. 2023 Feb; 24(4): 3863. Published online 2023 Feb 15. doi: 10.3390/ijms24043863

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