T cell-redirecting therapies in hematological malignancies: Current developments and novel strategies for improved targeting

Mol Ther. 2024 Sep 4;32(9):2856-2891. doi: 10.1016/j.ymthe.2024.07.028. Epub 2024 Aug 5.

Abstract

T cell-redirecting therapies (TCRTs), such as chimeric antigen receptor (CAR) or T cell receptor (TCR) T cells and T cell engagers, have emerged as a highly effective treatment modality, particularly in the B and plasma cell-malignancy setting. However, many patients fail to achieve deep and durable responses; while the lack of truly unique tumor antigens, and concurrent on-target/off-tumor toxicities, have hindered the development of TCRTs for many other cancers. In this review, we discuss the recent developments in TCRT targets for hematological malignancies, as well as novel targeting strategies that aim to address these, and other, challenges.

Keywords: CAR T cell; T cell engager; T cell-redirecting therapies; hematological malignancies; immunotherapy; on-target, off-tumor toxicities.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology
  • Hematologic Neoplasms* / immunology
  • Hematologic Neoplasms* / therapy
  • Humans
  • Immunotherapy, Adoptive* / methods
  • Receptors, Antigen, T-Cell* / immunology
  • Receptors, Antigen, T-Cell* / metabolism
  • Receptors, Chimeric Antigen* / immunology
  • Receptors, Chimeric Antigen* / metabolism
  • T-Lymphocytes* / immunology
  • T-Lymphocytes* / metabolism

Substances

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