Current state and next-generation CAR-T cells in multiple myeloma

Blood Rev. 2022 Jul;54:100929. doi: 10.1016/j.blre.2022.100929. Epub 2022 Jan 21.

Abstract

Chimeric antigen receptor T cells (CAR-T cells) have emerged as a potentially transformative new approach to treating hematological malignancies. Ide-cel, an autologous B cell maturation antigen (BCMA) targeting CAR-T cells, has recently been approved to treat multiple myeloma (MM). Here, we review the main clinical trials of CAR-T cells in MM with the most advanced autologous BCMA-directed ide-cel and cilta-cel, the human CARs orva-cel and CT053, the alternative manufacturing process with P-BCMA-101 and bb21217, the dual CAR GC012F and the allogenic BCMA-directed CAR-T cells ALLO-715. In light of those clinical data, we provide an overview of CAR-T cells' main potential resistance mechanisms, including antigen loss, antigen spreading, anti-CAR antibodies, CAR-T cell exhaustion, and the emergence of a non-permissive microenvironment. Finally, we describe the principal area of research to build the next generation of CAR-T cells, with armored-, gated- or commuting-CARs, CARs associated with knock out of specific genes, and CAR-T cells made from γδT cells or NK cells.

Publication types

  • Review

MeSH terms

  • B-Cell Maturation Antigen* / genetics
  • B-Cell Maturation Antigen* / therapeutic use
  • Humans
  • Immunotherapy, Adoptive
  • Multiple Myeloma* / pathology
  • Receptors, Chimeric Antigen
  • T-Lymphocytes
  • Tumor Microenvironment

Substances

  • B-Cell Maturation Antigen
  • Receptors, Chimeric Antigen
  • idecabtagene vicleucel