CL2A-SN-38 is a cleavable linker-based antibody-drug conjugate (ADC) containing the topoisomerase I inhibitor SN-38 and a maleimidocaproyl linker.1 CL2A-SN-38 has been linked to tumor-selective humanized antibodies, such as anti-Trop-2 (hRS7), to target SN-38 to tumor sites. CL2A-SN-38 linked to hRS7 is cytotoxic to Calu-3, COLO 205, Capan-1, PC3, SK-MES-1, and BxPC-3 cancer cells (IC50s =1.95-23.14 nM). CL2A-SN-38 linked to hRS7 reduces tumor growth in BxPC-3 pancreatic and SK-MES-1 lung cancer mouse xenograft models.
1.Cardillo, T.M., Govindan, S.V., Sharkey, R.M., et al.Humanized anti-Trop-2 IgG-SN-38 conjugate for effective treatment of diverse epithelial cancers: Preclinical studies in human cancer xenograft models and monkeysClin. Cancer Res.17(10)3157-3169(2011)