Targeting tumor microenvironment with antibody-guided IL-2 pro-cytokine promotes and rejuvenates dysfunctional CD8+ T cells

作者：Xue Wang, Longchao Liu, Tao Yue, Zhichen Sun, Joonbeom Bae, Kuo‐Fu Tseng, Anli Zhang, Jian Qiao, Yang‐Xin Fu · 发表于：Signal Transduction and Targeted Therapy · 年份：2023 · DOI：10.1038/s41392-023-01463-y · 被引用次数：9 · 研究领域：Cancer Immunotherapy and Biomarkers、Immunotherapy and Immune Responses、CAR-T cell therapy research

CLDN18.2 (CLDN), a member of tight junction protein family, is strictly limited to express on differentiated epithelial cells of the gastric mucosa and abnormal overexpression has been found in many cancers, especially in digestive system malignancies. 1 Those features make CLDN a potential therapeutic target. However, monoclonal antibody targeting CLDN induce limited antitumor immune responses in clinical trials and fusion of strong immunomodulators might be needed to enhance its efficacy. High dose IL-2 activates tumor infiltrating lymphocytes (TILs), but the severe toxicity and poor tumor targeting limits its use. 2