Affiliation:
1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Biochemistry and Molecular Biology Peking University Cancer Hospital & Institute Beijing China
2. Ningxia Human Stem Cell Research Institute The General Hospital of Ningxia Medical University Yinchuan China
3. Pathology Department of the First Affiliated Hospital Hainan Medical University Haikou China
Abstract
AbstractSince NKG2D ligands (NKG2DLs) are primarily overexpressed on multiple types of solid tumors but absent on most normal tissues, NKG2DLs could be optimal antigens for CAR‐T cells. To date, there have been two types of NKG2DL CARs: (i) the extracellular domain of NKG2D fused to the CD8a transmembrane domain, signaling domains of 4‐1BB and CD3ζ (NKBz) and (ii) full‐length NKG2D fused to the CD3ζ signaling domain (chNKz). Although NKBz‐ and chNKz‐engineered T cells both showed antitumor activities, a comparison of their functions has not been reported. In addition, use of the 4‐1BB signaling domain into the CAR construct could prolong the persistence and resistance to antitumor activities of CAR‐T cells, we designed a new NKG2DL CAR, full‐length NKG2D fused to the signaling domains of 4‐1BB and CD3ζ (chNKBz). Among the two types of NKG2DL CAR‐T cells reported in previous studies, we found that chNKz T cells had stronger antitumor ability than NKBz T cells in vitro, but their antitumor activity in vivo is similar. The chNKBz T cells showed antitumor activity superior to that of chNKz T cells and NKBz T cells in vitro and in vivo, providing a new option for the immunotherapy of NKG2DL‐positive tumor patients.
Funder
National Natural Science Foundation of China
Subject
Cell Biology,Immunology,Immunology and Allergy
Cited by
1 articles.
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