The role of chimeric antigen receptor T cells targeting more than one antigen in the treatment of B-cell malignancies

Br J Haematol. 2024 May;204(5):1649-1659. doi: 10.1111/bjh.19348. Epub 2024 Feb 16.

Abstract

Several products containing chimeric antigen receptor T cells targeting CD19 (CART19) have been approved for the treatment of patients with relapsed/refractory non-Hodgkin's lymphoma (NHL) and acute lymphoblastic leukaemia (ALL). Despite very impressive response rates, a significant percentage of patients experience disease relapse and die of progressive disease. A major cause of CART19 failure is loss or downregulation of CD19 expression in tumour cells, which has prompted a myriad of novel strategies aimed at targeting more than one antigen (e.g. CD19 and CD20 or CD22). Dual targeting can the accomplished through co-administration of two separate products, co-transduction with two different vectors, bicistronic cassettes or tandem receptors. In this manuscript, we review the pros and cons of each strategy and the clinical results obtained so far.

Keywords: ALL; CAR; CD19; CD20; CD22; NHL; dual.

Publication types

  • Review

MeSH terms

  • Antigens, CD19* / immunology
  • Antigens, CD20 / immunology
  • Antigens, Neoplasm / immunology
  • Humans
  • Immunotherapy, Adoptive* / methods
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Chimeric Antigen* / immunology
  • Sialic Acid Binding Ig-like Lectin 2 / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Receptors, Chimeric Antigen
  • Antigens, CD19
  • Receptors, Antigen, T-Cell
  • Antigens, CD20
  • CD19 molecule, human
  • Antigens, Neoplasm
  • Sialic Acid Binding Ig-like Lectin 2