Abstract 912: CLDN6 and CLDN9 dual targeting antibody drug conjugates for the treatment of ovarian and endometrial cancers

Abstract

Abstract Claudins (CLDNs) are tight junction proteins that regulate epithelial-cell barrier function and polarity. Up-regulation of certain CLDN proteins has been associated with the malignant phenotype. Embryonic, stem-cell specific CLDN6 is absent in normal adult tissues. Our in-house data showed that it is highly expressed in serous ovarian (66% cases showed 2+/3+/4+ expression of CLDN6), and testis cancers (100% cases showed 4+ expression of CLDN6) in Chinese population, and is an “ideal” target in these cancer types. CLDN9, sharing high homology with CLDN6 exhibits similar distribution patterns with CLDN6, like the absence in normal tissues and up-regulation in ovarian and endometrial cancer. We propose to simultaneously target both CLDN6 and CLDN9 for treatment of ovarian cancer and endometrial cancer to achieve better anti-tumor efficacy and expand the treatment to a larger population of patients. To this end, we designed a high-through-put antibody screening process and discovered two antibodies GB7008-03 and GB7008-05, both of which binds CLDN6 and CLDN9 with high affinity, while sparing other CLDN members. Both candidates demonstrated superior antibody-mediated antigen internalization than ASP1650, the forerunner in clinical trials. GB7008-03 and GB7008-05 also showed good ADCC potency on CLDN6 expressing tumor cell lines. Currently we are developing antibody-drug-conjugates based on these two antibodies. In vivo efficacy of these ADCs in CDX models will be presented. Citation Format: Liang Du, Hongyan Zhang, Lina Jin, Yali Chen, Tingting Wan, Liuliu Xu. CLDN6 and CLDN9 dual targeting antibody drug conjugates for the treatment of ovarian and endometrial cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 912.