Article ; Online: T cells engineered with full-length NKG2D linked to signaling domains of 4-1BB and CD3ζ show enhanced antitumor activity.
2023 Volume 101, Issue 5, Page(s) 458–464
Abstract: Since 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 ... ...
| Abstract | Since 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. |
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| MeSH term(s) | Humans ; Cell Line, Tumor ; Immunotherapy ; Immunotherapy, Adoptive ; Neoplasms ; NK Cell Lectin-Like Receptor Subfamily K ; Signal Transduction ; T-Lymphocytes ; Xenograft Model Antitumor Assays ; 4-1BB Ligand/metabolism |
| Chemical Substances | NK Cell Lectin-Like Receptor Subfamily K ; 4-1BB Ligand ; CD3 antigen, zeta chain |
| Language | English |
| Publishing date | 2023-03-10 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 284057-1 |
| ISSN | 1440-1711 ; 0818-9641 |
| ISSN (online) | 1440-1711 |
| ISSN | 0818-9641 |
| DOI | 10.1111/imcb.12634 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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