The potential of γδ CAR and TRuC T cells: An unearthed treasure

  • Eur J Immunol. 2024 Nov;54(11):e2451074. doi: 10.1002/eji.202451074.
Wolfgang W Schamel  1  2  3 ,  Marina Zintchenko  1  2 ,  Trang Nguyen  1  2  4 ,  Boris Fehse  5  6 ,  Priscilla S Briquez  7 ,  Susana Minguet  1  2  3
Affiliations
  • 1. Signaling Research Centres BIOSS and CIBSS; Department of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany.
  • 2. Department of Immunology, Faculty of Biology, University of Freiburg, Freiburg, Germany.
  • 3. Centre for Chronic Immunodeficiency (CCI), Faculty of Medicine, University Clinics Freiburg, Freiburg, Germany.
  • 4. Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany.
  • 5. Research Department Cell and Gene Therapy, Department of Stem Cell Transplantation, and Hamburg Centre for Translational Immunology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
  • 6. Hamburg Centre for Translational Immunology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
  • 7. Department of General and Visceral Surgery, Faculty of Medicine, Medical Center - University of Freiburg, Freiburg, Germany.
Abstract

Recent years have witnessed the success of αβ T cells engineered to express chimeric antigen receptors (CARs) in treating haematological cancers. CARs combine the tumour antigen binding capability of antibodies with the signalling functions of the T-cell receptor (TCR) ζ chain and co-stimulatory receptors. Despite the success, αβ CAR T cells face limitations. Possible solutions would be the use of γδ T cells and new chimeric receptors, such as TCR fusion constructs (TRuCs). Notably, γδ CAR T cells are gaining traction in pre-clinical and clinical studies, demonstrating a promising safety profile in several pilot studies. This review delves into the current understanding of γδ CAR and TCR fusion construct T cells, exploring the opportunities and challenges they present for Cancer treatment.

Keywords
CAR; Immunotherapy; TRuC; Tumour; γδ T cell.