Advancements in the design and function of bispecific CAR-T cells targeting B Cell-Associated tumor antigens

Int Immunopharmacol. 2024 Dec 5;142(Pt B):113166. doi: 10.1016/j.intimp.2024.113166. Epub 2024 Sep 18.

Abstract

Single-targeted CAR-T has exhibited notable success in treating B-cell tumors, effectively improving patient outcomes. However, the recurrence rate among patients remains above fifty percent, primarily attributed to antigen escape and the diminished immune persistence of CAR-T cells. Over recent years, there has been a surge of interest in bispecific CAR-T cell therapies, marked by an increasing number of research articles and clinical applications annually. This paper undertakes a comprehensive review of influential studies on the design of bispecific CAR-T in recent years, examining their impact on bispecific CAR-T efficacy concerning disease classification, targeted antigens, and CAR design. Notable distinctions in antigen targeting within B-ALL, NHL, and MM are explored, along with an analysis of how CAR scFv, transmembrane region, hinge region, and co-stimulatory region design influence Bi-CAR-T efficacy across different tumors. The summary provided aims to serve as a reference for designing novel and improved CAR-Ts, facilitating more efficient treatment for B-cell malignant tumors.

Keywords: B-cell tumors; Bispecific CAR-T; CAR-T; Design; Function.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigens, Neoplasm* / immunology
  • B-Lymphocytes* / immunology
  • Humans
  • Immunotherapy, Adoptive* / methods
  • Receptors, Chimeric Antigen* / genetics
  • Receptors, Chimeric Antigen* / immunology
  • T-Lymphocytes / immunology

Substances

  • Receptors, Chimeric Antigen
  • Antigens, Neoplasm