Preclinical assessment of the efficacy of B7-H3 CAR-T in renal cell carcinoma

Mol Immunol. 2024 Dec:176:1-10. doi: 10.1016/j.molimm.2024.10.006. Epub 2024 Nov 7.

Abstract

B7-H3 is a type I transmembrane protein that belongs to the B7 immune checkpoint protein family, is aberrantly expressed in cancer cells, but rarely expressed in normal tissues, making it an attractive target for cancer therapy. Here, we found B7-H3 is highly expressed in the renal cell carcinoma (RCC) tumor tissues and RCC cell lines, but is undetectable in normal renal tissues. Therefore, we engineered second-generation CAR-T cells targeting B7-H3, incorporating either CD28 or 4-1BB co-stimulatory domains. Both CAR-T cell variants demonstrated potent antitumor activity against RCC tumors in vitro and in metastatic and orthotopic RCC mouse models. Furthermore, the B7-H3 CAR-T cells exhibited remarkable proliferation and robust cytokine release when co-cultured with RCC cancer cells. These findings demonstrated that targeting B7-H3 by CAR-T cells potentially offering a new treatment option for RCC patients.

Keywords: B7-H3; CAR-T; Renal cell carcinoma.

MeSH terms

  • Animals
  • B7 Antigens* / immunology
  • B7 Antigens* / metabolism
  • Carcinoma, Renal Cell* / immunology
  • Carcinoma, Renal Cell* / pathology
  • Carcinoma, Renal Cell* / therapy
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Humans
  • Immunotherapy, Adoptive* / methods
  • Kidney Neoplasms* / immunology
  • Kidney Neoplasms* / pathology
  • Kidney Neoplasms* / therapy
  • Mice
  • Receptors, Chimeric Antigen* / immunology
  • T-Lymphocytes / immunology
  • Xenograft Model Antitumor Assays

Substances

  • B7 Antigens
  • CD276 protein, human
  • Receptors, Chimeric Antigen