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 4-1BB knock-in (B-h4-1BB) mice were generated with a chimeric 4-1BB receptor, which is recognizable by stimulatory human 4-1BB antibodies. Additionally, more knock-in mice targeting stimulatory immune checkpoint molecules were developed and validated, such as B-hCD3e, B-hCD40, B-hOX40, B-hGITR, B-hCD27, B-hCD28 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.
Clinical trial identification
Legal entity responsible for the study
Beijing Biocytogen Co., Ltd.
Has not received any funding.
All authors have declared no conflicts of interest.