Novel anti-CD40 Antibodies Demonstrate Anti-tumor Activity in Humanized Mouse Models

Novel anti-CD40 Antibodies Demonstrate Anti-tumor Activity in Humanized Mouse Models

Author: Chaoshe Guo, Jian Ni, Benny Yang, Yanan Guo, Tian Gan

AACR Annual Meeting 2019 # 3241CD40, Cluster of Differentiation 40, is a member of the TNF-receptor superfamily. Whereas most immune checkpoint receptors are expressed on the surface of T cells, CD40 stands out as it is expressed by antigen presenting cells and controls the proper activation of these cells. In turn, CD40 activation exerts a significant impact on T cell-mediated activity against cancer cells.

We have interests in developing novel CD40 antibodies for boosting cancer patients’ own immunity considering other successful immune checkpoint modulators. We asked whether we could find suitable anti-CD40 reagents which can successfully combat developed tumors in preclinical settings. We designed a powerful screening strategy on Biocytogen’s in vivo drug screening platform. Candidate antibodies were generated by immunizing wild-type mice with recombinant hCD40 protein. Then the hybridomas were screened by high-throughput flow cytometry. Instead of examining the immune modulating activity in cell culture, we applied these antibodies to B-hCD40 mice bearing MC38 tumors and monitored the tumor growth. Through this straightforward screening, several clones stood out by their unparalleling benefits. These clones were further selected for humanization. Furthermore, we identified that one clone works in concert with Keytruda in the dual humanized model of h-CD40 and h-PD1. In the end, we discovered the leads with the most potent anti-tumor activity. In conclusion, our work successfully identified several novel CD40 antibodies that are highly effective for cancer treatment in the preclinical setting.

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