Abstract B052: Immunotherapy for melanoma by adenovirus-mediated full-length antibody, nivolumab

Abstract

Abstract Nivolumab, a fully human, IgG4 immune checkpoint inhibitor antibody, binds PD-1 on activated immune cells to disrupt PD-1 interaction with PD-L1 and PD-L2 ligands, thereby attenuating inhibitory signals and augmenting the host antitumour response. In 2014, nivolumab was approved by FDA and has been used to treat various types of cancer such as melanoma, non-small cell lung cancer, renal cell carcinoma, and classic Hodgkin's lymphoma. However, due to the high price of nivolumab and the long cycle of treatment, many patients cannot afford and receive adequate treatment. Here, we generated a new, cheaper form of nivolumab for cancer immunotherapy, by cloning the full-length nivolumab antibody gene into two serotypes of adenovirus vectors, termed as AdHu5-Nivo and AdC68-Nivo. Ad vectors based on human serotype 5 (AdHu5) have been proved in a lot of previous studies to be safe and efficient. Compared with AdHu5, chimpanzee Ads exhibit much lower seroprevalence in human beings, which made them great alternative Ad gene vector. Until now, we have detected a high expression of nivolumab in vitro by Western blot and sandwich ELISA. In vivo studies showed that a single dose of AdHu5-Nivo or AdC68-Nivo can induce sustained nivolumab expression. The biologic activities of the two mAbs are analogous compared with commercial monoclonal antibody. To follow up we will verify their antitumor effects on both cellular level and melanoma transplant animal models. Citation Format: Xuchen Wang. Immunotherapy for melanoma by adenovirus-mediated full-length antibody, nivolumab [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B052.