Icos-Expressing Car-T Cells Mediate Durable Eradication of Triple-Negative Breast Cancer and Metastasis

Authors

Shelley Herbrich
Mehdi Chaib
Padmanee Sharma

Publication Date

3-18-2025

Journal

The Journal for ImmunoTherapy of Cancer

Abstract

Triple-negative breast cancer (TNBC) remains one of the most aggressive and therapeutically challenging breast cancer subtypes. In their recent study, Cao et al introduced a B7H3-specific chimeric antigen receptor (CAR)-T cell with constitutive inducible co-stimulator (ICOS) expression (ICOS-B7H3-CAR-T), which demonstrated eradication of TNBC, including metastases, in preclinical models. These CAR-T cells exploit the expression of ICOS ligand on TNBC cells, enhancing antitumor cytotoxicity through ICOS signaling. Compared with conventional B7H3-CAR-T cells, the ICOS-B7H3-CAR-T cells exhibited superior antitumor efficacy, increased cytokine secretion, and prolonged survival in xenograft murine models. This study highlights ICOS as a promising co-stimulatory molecule for improving CAR-T therapy against solid tumors and underscores the critical role of ICOS signaling in enhancing therapeutic outcomes. Here, we discuss the implications of these findings for TNBC treatment, the importance of understanding and exploiting ICOS biology in immunotherapies, and future directions for optimizing ICOS CAR-T cell therapies in solid tumor immunotherapy.

Keywords

Triple Negative Breast Neoplasms, Humans, Inducible T-Cell Co-Stimulator Protein, Animals, Female, Immunotherapy, Adoptive, Mice, Receptors, Chimeric Antigen, Neoplasm Metastasis, T-Lymphocytes, Breast Cancer, Chimeric antigen receptor - CAR, Immunotherapy

DOI

10.1136/jitc-2025-011564

PMID

40107673

PMCID

PMC11927425

PubMedCentral® Posted Date

3-18-2025

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes