When de novo-designed protein logics meet CAR-T therapies

• 来源期刊: 细胞研究（英文版）
• 年，卷（期）: 2020,（11）
• 所属期刊栏目: RESEARCH HIGHLIGHTS
• 页码范围: 946-947
• 页数: 2页
• 语种: 英文

摘要

Protein logic gates acting at posttranscriptional levels are unique in being amenable to the control of both intracellular and intercellular biological processes.In a recent paper published in Science, Lajoie et al.engineered highly versatile colocalization-dependent protein switch that are activated upon detection of logic combinations (e.g., AND, OR and NOT)of specific cell surface antigens, providing another important asset for "universal" CAR-T therapies. In recent years, chimeric antigen receptor T cell (CAR-T)therapies based on adoptive transfer of ex vivo engineered patient-specific T cells have finally arrived on the central stage of the pharmaceutical industry.1 Despite showing excellent response rates in many patients suffering from blood tumors (e.g.,leukemia), many hurdles still need to be overcome to accelerate the development of future CAR-T therapies.2 One major challenge is that, in many cases, multiple cell surface antigens are required to confidently distinguish tumor cells from healthy tissues.3 In addition, selection and clinical validation of monoclonal antigen-specific CAR-T cells are highly time and resource intensive.Technologies that can avoid tumor-specific re-engineering of the T cells would therefore be heavily needed.