Abstract 5694: Evaluation of the in vivo efficacy of immune-oncology drugs targeting stimulatory immune checkpoint molecules using humanized knock-in mice

Abstract

Abstract Cancer immunotherapy is one of the most promising research areas in the field of cancer therapy. Many pharmaceutical and biotech companies in the world are devoting great effort to develop cancer immunity-related treatment antibodies. However, along the IO drug development process, in vivo efficacy models have always been a rate-limiting step. In most cases, a human monoclonal antibody does not have mouse cross-reactivity. Mouse surrogate antibodies were often used in immune-competent syngeneic mouse models to evaluate in vivo efficacy of IO drugs. However, the efficacy of a surrogate antibody cannot fully represent the human drug in the clinical scenario. Therefore, we generated humanized knock-in mice to evaluate the in vivo efficacy of human IO antibodies. For example, human OX40 knock-in (B-hOX40) mice were generated with a chimeric OX40 receptor, which is recognizable by stimulatory human OX40 antibodies. Additionally, more knock-in mice targeting stimulatory immune checkpoint molecules were developed and validated, such as B-hCD137, B-hGITR, B-hCD27, B-hCD40, B-hCD28, B-hCD3 et al,. All these mouse models response well to the corresponding human IO antibodies, proving that they are powerful tools for in vivo efficacy evaluation of human stimulatory immune checkpoint antibodies. Citation Format: Tongmei Xia, Chaoshe Guo, Yuelei Shen, Yanan Guo. Evaluation of the in vivo efficacy of immune-oncology drugs targeting stimulatory immune checkpoint molecules using humanized knock-in mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5694.