cBR96-doxorubicin immunoconjugate (BMS-182248/SGN-15; also known as cBR96-Dox) is an antibody-drug conjugate or (ADC) directed to the Lewis-Y antigen designed for the treatment of cancer. The payload is the chemotherapy drug doxorubicin which is connected with a hydrazone linker to cysteine residues of the Lewis-Y specific (chimeric) monoclonal antibody BR96.[1] Following internalization, the hydrazone is hydrolyzed within the acidic environment of target cell endosomes and lysosomes to release active cytotoxic drug.
| Monoclonal antibody | |
|---|---|
| Type | ? |
| Source | Humanized (from mouse) |
| Target | Lewis-Y antigen |
| Clinical data | |
| Other names | SGN-15, BMS-182248 |
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Clinical Development
editIn clinical trials cBR96-Dox was found to be highly active in regressing large human tumor xenografts implanted in mice or rats.[2][3] Multiple tumor models including lung, breast and colon were evaluated, and cBR96-Dox was found to have broad and potent anti-tumor activity, even in doxorubicin-resistant tumors.
References
edit- ^ Hofland P (2013). "Harnessing The Power of Three: Advancing Antibody-drug Conjugates from Laboratory to Bedside". ADC Review / Journal of Antibody-drug Conjugates. 1. doi:10.14229/jadc.2013.6.1.001.
- ^ Trail PA, Willner D, Lasch SJ, Henderson AJ, Hofstead S, Casazza AM, Firestone RA, Hellström I, Hellström KE (July 1993). "Cure of xenografted human carcinomas by BR96-doxorubicin immunoconjugates". Science. 261 (5118): 212–5. Bibcode:1993Sci...261..212T. doi:10.1126/science.8327892. PMID 8327892.
- ^ Sjögren HO, Isaksson M, Willner D, Hellström I, Hellström KE, Trail PA (October 1997). "Antitumor activity of carcinoma-reactive BR96-doxorubicin conjugate against human carcinomas in athymic mice and rats and syngeneic rat carcinomas in immunocompetent rats". Cancer Research. 57 (20): 4530–6. PMID 9377565.