Tandem CAR-T cells targeting MUC1 and PSCA combined with anti-PD-1 antibody exhibit potent preclinical activity against non-small cell lung cancer

Cell Immunol. 2023 Sep-Oct:391-392:104760. doi: 10.1016/j.cellimm.2023.104760. Epub 2023 Aug 29.

Abstract

Chimeric antigen receptor (CAR)-T cells encounter many issues when treating solid tumors, including tumor antigen heterogeneity and immunosuppression. United targeting of two tumor-associated antigens (TAAs) and blocking of PD-1 may solve this problem and enhance the function of CAR-T. Mucin 1 (MUC1) and prostate stem cell antigen (PSCA) are overexpressed in non-small cell lung cancer (NSCLC). Here, we constructed a bivalent tandem CAR-T (Tan CAR-T), which can simultaneously target MUC1 and PSCA and evaluated its effects of inhibiting non-small cell lung cancer (NSCLC) in vitro and in vivo. Results indicated that the tumor killing effect of these Tan CAR-T was more effective than that of single-target CAR-T, its antitumor efficacy could be further strengthened by anti-PD-1 antibody. Our study reported a previously unstudied therapeutic effect of a Tan CAR-T in NSCLC, providing a preclinical rationale for anti-PD-1 antibody combined with Tan CAR-T targeting MUC1 and PSCA in the treatment of NSCLC.

Keywords: Anti-PD-1 antibody; MUC1; NSCLC; PSCA; Tandem CAR-T.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm
  • Carcinoma, Non-Small-Cell Lung* / therapy
  • Cell Line, Tumor
  • GPI-Linked Proteins
  • Humans
  • Immunotherapy, Adoptive / methods
  • Lung Neoplasms* / therapy
  • Male
  • Mucin-1
  • Neoplasm Proteins
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen*
  • T-Lymphocytes

Substances

  • Mucin-1
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen
  • Antigens, Neoplasm
  • MUC1 protein, human
  • PSCA protein, human
  • Neoplasm Proteins
  • GPI-Linked Proteins