Pre-depletion of TRBC1+ T cells promotes the therapeutic efficacy of anti-TRBC1 CAR-T for T-cell malignancies

Mol Cancer. 2020 Nov 21;19(1):162. doi: 10.1186/s12943-020-01282-7.

Abstract

Targeting T cell receptor β-chain constant region 1 (TRBC1) CAR-T could specifically kill TRBC1+ T-cell malignancies. However, over-expressed CARs on anti-TRBC1 CAR transduced TRBC1+ T cells (CAR-C1) bound to autologous TRBC1, masking TRBC1 from identification by other anti-TRBC1 CAR-T, and moreover only the remaining unoccupied CARs recognized TRBC1+ cells, considerably reducing therapeutic potency of CAR-C1. In addition, co-culture of anti-TRBC1 CAR-T and TRBC1+ cells could promote exhaustion and terminal differentiation of CAR-T. These findings provide a rationale for pre-depleting TRBC1+ T cells before anti-TRBC1 CAR-T manufacturing.

Keywords: CAR-T; T cell receptor β-chain constant region 1; T-cell malignancy.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Proliferation
  • Cytotoxicity, Immunologic / immunology*
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Leukemia, T-Cell / immunology
  • Leukemia, T-Cell / metabolism
  • Leukemia, T-Cell / pathology
  • Leukemia, T-Cell / therapy*
  • Lymphocyte Depletion / methods*
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Chimeric Antigen / immunology
  • T-Lymphocytes / immunology*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen