Cantuzumab mertansine

Cantuzumab mertansine (SB-408075; huC242-DM1), an ADC, is an immunoconjugate of the potent maytansine derivative (DM1; HY-19792) and the humanized monoclonal antibody (huC242) directed to CanAg. Cantuzumab mertansine has cytotoxic toward colon cancer cells and has broad antitumor efficacy against a range of CanAg-positive human tumor xenografts[1][2].

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> Microtubule/Tubulin

Signaling Pathways >> Cytoskeleton >> Microtubule/Tubulin

Cantuzumab mertansine (SB-408075; huC242-DM1; 0-100 μM; 24 h) has selective cytotoxic activity on antigen-positive COLO 205 cell line[1]. Cell Cytotoxicity Assay[1] Cell Line: Antigen-positive COLO 205 cell line and the antigen-negative A-375 melanoma cell line Concentration: 0-100 μM Incubation Time: 24 h Result: Had cytotoxic activity on COLO 205 cells with an IC50 value of 0.032 nM (23.5 pg/ml). Had 1100-fold less cytotoxic activity for the antigen-negative A-375 cells (IC50=36 nM; 26.5 ng/ml).

Cantuzumab mertansine (SB-408075; huC242-DM1; 300 μg/kg/day for 5 days) resultes in complete regressions and cures of mice bearing human xenografts of Colo 205 colon cancer[1]. Animal Model: Female CB-17 SCID mice, 6-7 weeks of age bearing COLO 205 human colon tumor xenografts[1] Dosage: 300 μg/kg Administration: Daily for 5 days Result: Completely eliminated any measurable tumors within 2 weeks of the initiation of therapy, and all eight animals were tumor-free for 200 days (duration of the experiment).

[1]. Paul R Helft, et al. A phase I study of cantuzumab mertansine administered as a single intravenous infusion once weekly in patients with advanced solid tumors. Clin Cancer Res. 2004 Jul 1;10(13):4363-8.  

[2]. Anthony W. Tolcher, et al. Cantuzumab Mertansine, a Maytansinoid Immunoconjugate Directed to the CanAg Antigen: A Phase I, Pharmacokinetic, and Biologic Correlative Study. J Clin Oncol. 2003 Jan 15;21(2):211-22.