Antibody-drug conjugates targeting DDR1 as a novel strategy for treatment of breast cancer

Abstract

Antibody-drug conjugates (ADCs) have emerged as a novel class of targeted cancer therapies and been successfully applied in the treatment of breast cancer (BC). Discoidin domain receptor 1 (DDR1) is a single transmembrane receptor tyrosine kinase and has been identified as a possible target for cancer. In this study, we explored the potential of an anti-DDR1 ADC, named T₄H₁₁-DM4, for the treatment of DDR1-positive BC. We demonstrated that high protein expression and RNA expression of DDR1 in BC tissues. In vitro, T₄H₁₁-DM4 was potently cytotoxic to DDR1-expressing BC cells, with IC50 in the nanomolar range. In mice BC xenograft models, T₄H₁₁-DM4 dramatically eliminated BC tumors, without observable toxicity. Taken together, our findings demonstrated that DDR1 can serve as a promising therapeutic target for BC.

Keywords:

• targeted cancer therapy
• antibody-drug conjugate
• discoidin domain receptor 1
• breast cancer

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Additional information

Funding

This work was supported by the National Natural Science Foundation of China (82073318 and 82104018).