| Monoclonal antibody | |
|---|---|
| Type | ? |
| Source | Humanized (from mouse) |
| Target | Lewis-Y antigen |
| Clinical data | |
| Other names | SGN-15, BMS-182248 |
| ATC code |
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| Identifiers | |
| CAS Number | |
| ChemSpider |
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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. Following internalization, the hydrazone is hydrolyzed within the acidic environment of target cell endosomes and lysosomes to release active cytotoxic drug.
Clinical Development
In clinical trials cBR96-Dox was found to be highly active in regressing large human tumor xenografts implanted in mice or rats. 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
- 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.