Dual-mechanism anti-CD73 antibodies CR201 and CR202 targeting distinct domains for cancer immunotherapy

By
Miao Zhang
Haibin Yuan
Xindi Pan
Xian Li
Zichen Wang
Shuping Zhang
Zhigang Gu
Biao Hu
Xuedong Qu
Qian Wang
Xiangguo Gu
Bo Wang
Yu Cao
Guilin Mu
Guangbo Kang
Ario de Marco
Xiangshan Zhou
He Huang
June 10, 2026
0 min

Frontiers In Immunology

Overview

CR201 and CR202 are novel anti-CD73 monoclonal antibodies that inhibit enzymatic activity and promote receptor internalization, enhancing cancer immunotherapy. Both antibodies demonstrated significant efficacy in suppressing tumor growth in preclinical models without observable toxicity.

Background

CD73 plays a critical role in the adenosine-mediated immunosuppressive pathway, which is a significant barrier to effective cancer immunotherapy. Targeting CD73 has emerged as a promising strategy to enhance antitumor immune responses by disrupting the accumulation of adenosine in the tumor microenvironment. The development of dual-mechanism antibodies like CR201 and CR202 aims to improve therapeutic outcomes in cancer treatment.

Data Highlights

Antibody	Target Domain	Activity
CR201	C-terminal	Complete inhibition of soluble CD73
CR202	N-terminal	Greater potency against membrane-bound CD73

Key Findings

CR201 and CR202 bind specifically to human and cynomolgus CD73.
CR202 targets the N-terminal domain, while CR201 targets the C-terminal domain of CD73.
Both antibodies restored T-cell proliferation and IFN-γ production in functional assays.
In vivo studies showed significant tumor growth suppression with either antibody.
No observable toxicity was reported with the administration of CR201 or CR202.

Clinical Implications

The development of CR201 and CR202 highlights the potential for dual-mechanism antibodies to enhance the efficacy of cancer immunotherapy. Their ability to inhibit both soluble and membrane-bound CD73 may provide a more effective strategy to overcome adenosine-mediated immunosuppression in tumors.

Conclusion

CR201 and CR202 represent promising advancements in the targeting of CD73 for cancer immunotherapy, integrating enzymatic blockade with receptor internalization to enhance immune responses against tumors.