MDX-1203 (BMS-936561) is an antibody-drug conjugate targeting CD70. MDX-1203 binds to CD70 and mediates the specific delivery of its conjugated cytotoxic payload to tumors. MDX-1203 delivers a DNA alkylating payload into cells. MDX-1203 can be used in research related to advanced clear cell renal cell carcinoma and relapsed/refractory B-cell non-Hodgkin lymphoma [1] [2].
In Vivo, MDX-1203 (4-38 mg/kg; single dose, 2 doses) exhibits dose-dependent efficacy in a murine 786-O renal cell carcinoma xenograft model, with complete tumor regression achieved with two 38 mg/kg doses[2]. MDX-1203 (10-100 mg/kg; i.v.; single dose, every 2 weeks; 3 doses) is safe at single 25 mg/kg and 100 mg/kg intravenous doses and repeated 10 mg/kg and 25 mg/kg intravenous doses every 2 weeks for 3 doses in Rattus norvegicus, but a single 50 mg/kg intravenous dose causes severe toxicity[2]. MDX-1203 (50 mg/kg; i.v.; repeated doses) is well tolerated in cynomolgus monkeys[2].
In Vitro, MDX-1203 binds CD70 with nanomolar affinity, induces dose-dependent cell death in CD70-expressing human tumor cell lines, and mediates antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) following internalization[2].
References:
[1]. Sung J, et al. In vitro plasma stability of human anti-CD70 antibody drug conjugate, MDX-1203[J]. Cancer Research, 2010, 70(8_Supplement): 2587-2587.
[2]. Owonikoko TK, et al. First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70. Cancer Chemother Pharmacol. 2016;77(1):155-162.
In Vivo, MDX-1203 (4-38 mg/kg; single dose, 2 doses) exhibits dose-dependent efficacy in a murine 786-O renal cell carcinoma xenograft model, with complete tumor regression achieved with two 38 mg/kg doses[2]. MDX-1203 (10-100 mg/kg; i.v.; single dose, every 2 weeks; 3 doses) is safe at single 25 mg/kg and 100 mg/kg intravenous doses and repeated 10 mg/kg and 25 mg/kg intravenous doses every 2 weeks for 3 doses in Rattus norvegicus, but a single 50 mg/kg intravenous dose causes severe toxicity[2]. MDX-1203 (50 mg/kg; i.v.; repeated doses) is well tolerated in cynomolgus monkeys[2].
In Vitro, MDX-1203 binds CD70 with nanomolar affinity, induces dose-dependent cell death in CD70-expressing human tumor cell lines, and mediates antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) following internalization[2].
References:
[1]. Sung J, et al. In vitro plasma stability of human anti-CD70 antibody drug conjugate, MDX-1203[J]. Cancer Research, 2010, 70(8_Supplement): 2587-2587.
[2]. Owonikoko TK, et al. First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70. Cancer Chemother Pharmacol. 2016;77(1):155-162.