CBR96-doxorubicin immunoconjugate explained

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.

Clinical Development

In 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.

Notes and References

1. Hofland P . Harnessing The Power of Three: Advancing Antibody-drug Conjugates from Laboratory to Bedside . 10.14229/jadc.2013.6.1.001 . ADC Review / Journal of Antibody-drug Conjugates . 2013 . 1 .
2. Trail PA, Willner D, Lasch SJ, Henderson AJ, Hofstead S, Casazza AM, Firestone RA, Hellström I, Hellström KE . Cure of xenografted human carcinomas by BR96-doxorubicin immunoconjugates . Science . 261 . 5118 . 212–5 . July 1993 . 8327892 . 10.1126/science.8327892 . 1993Sci...261..212T .
3. Sjögren HO, Isaksson M, Willner D, Hellström I, Hellström KE, Trail PA . 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 . October 1997 . 9377565 .