Abstract 1214: Development of anti-5T4 antibody-drug conjugates, ZV05-ADCs for targeted cancer therapy in different type of cancers

Abstract

5T4 is an N-glycosylated transmembrane 72 kDa glycoprotein expressed in a number of carcinomas, and has been explored as a target for cancer therapy in different type of cancers, including NSCLC, RCC, colorectal, ovarian, pancreatic and gastric cancers. The expression of 5T4 in normal tissue is very limited, but widespread in malignant tumors throughout their development, making it an attractive target for antibody-drug conjugate (ADC). In this aspect, a 5T4-MMAF ADC from Pfizer is under clinical investigation in phase I/II trials. We have developed novel anti-5T4 ADCs, using our proprietary conjugation technologies. A highly potent anti-5T4 antibody ZV05 was conjugated to a variety of internally developed linkers and toxins and purified to populations containing defined DAR (Drug-Antibody Ratio) numbers. The ADCs were studied both in vitro and in vivo for their activity against a variety of tumors. The results showed that the lead ZV05 ADCs were potent towards a bunch of cancer cell lines that express 5T4, and also dramatically inhibited tumor growth in several models in vivo. In the xenograft studies, a single dose of the lead ZV05 ADCs completely wiped out the tumors and kept the tumor volume down for the whole period of studies. ZV05 ADCs are currently under further evaluation to select a candidate for clinical treatment of 5T4-positive cancers. Citation Format: Zhaohui Li, Zhangming Xie, Qian Zhang, Jie Fang, Liqin Wu, Hedi Fang, Hong Zhang, Tong Zhu, Gang Chen, David Miao, Sheldon Cao. Development of anti-5T4 antibody-drug conjugates, ZV05-ADCs for targeted cancer therapy in different type of cancers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1214.