We found elevated CD73 expression to be prevalent in non–small cell lung cancer (NSCLC) including those harboring the RAS- or RTK (EGFR, EML4-ALK) oncogenes. CD73 expression is enriched closely with the transcriptome signature of epithelial–mesenchymal transition and the immune-tolerant tumor microenvironment, which are increasingly relevant for disease progression and therapy resistance. We developed two novel series of CD73 antibody, Ab001/Ab002 and humanized version Hu001/Hu002, which demonstrated high CD73 binding affinity, potent enzyme inhibition, and efficiently protected effector T lymphocyte function from adenosine/cancer-imposed toxicity. Hu001/Hu002 inhibited growth of RAS-mutant NSCLC tumors in mice via enhanced antibody-dependent cell-mediated cytotoxicity and multifaceted remodeling of the tumor immune environment, reflecting diminished levels of tumor-associated macrophages, myeloid-derived suppressor cells, and tumor vasculature. A novel MMAE-conjugated CD73-ADC (Hu001–..... READ ARTICLE

Molecular Cancer Therapeutics DOI: 10.1158/1535-7163.MCT-20-0076

Authors: Rui Jin, Liang Liu, Yun Xing, Tao Meng, Lanping Ma, Jinpeng Pei, Ying Cong, Xuesai Zhang, Zhiqiang Ren, Xin Wang, Jingkang Shen and Ker Yu