HONG KONG, April 14, 2022 /PRNewswire/ -- Akeso, Inc. (9926. HK) ( "Akeso" ), a China-based biopharmaceutical company focusing on the development and commercialization of innovative therapeutic antibodies for Oncology & Immunology, announced the publication of preclinical results of its PD-1/CD73 bi-specific antibody (AK131) at the American Association for Cancer Research (AACR) Annual Meeting 2022. AK131 has been demonstrated to have potent in-vitro and in-vivo anti-tumor activities.
Abstract: AK131, an anti-PD1/CD73 bispecific antibody for cancer immune therapy
AK131 is a bi-specific antibody derived from Penpulimab (Akeso's marketed PD-1 antibody ) and AK119 (Akeso's CD73 antibody in the clinical stage). AK119 is a dual mechanism antibody (2021 SITC poster #750) that both blocks the generation of adenosine and stimulates antigen-specific B cell activation. Adenosine is a key immune suppressive molecule contributing to the resistance of PD-1 antibody therapy. Both CD73 and PD-1 are with high expression in the tumor microenvironment. Moreover, a growing body of literature evidence supports an important role of B cells in anit-tumor immunity. Thus the company developed a bi-specific PD-1/CD73 antibody with the capacity to relieve immune checkpoint control of T cells, activate B cells, and eliminate immune suppression by adenosine, for immune therapy of cancer.
The results and observations in AK131's preclinical study support the development of AK131 as an anti-tumor agent in the clinic：
- AK131 is effectively bound to human PD-1 and CD73 with high affinity. The interaction between PD-1 and its ligand PD-L1 was blocked by AK131 in the reporter gene assay.
- In cellular assays, AK131 effectively promoted the secretion of IFN-γ and IL-2 by T cells in the co-culture of PBMCs and Raji-PDL1 cells.
- Moreover, AK131 inhibited CD73 enzymatic activity and induced endocytosis of CD73. AK131 enhanced the expression of CD69, CD83, HLA-DR, and IgM which are markers of B cell activation in an adenosine-independent manner.
- In in-vivo assay, AK131 successfully inhibited tumor growth in C57BL/6-hPD1/hPDL1/hCD73 transgenic mice MC38-hPDL1-hCD73 tumor syngeneic model.
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