Current progress in chimeric antigen receptor-modified T cells for the treatment of metastatic breast cancer

Breast cancer is the leading cancer in women. Around 20-30% breast cancer patients undergo invasion or metastasis after radical surgical resection and eventually die. Number of breast cancer patients show poor sensitivity toward treatments despite the advances in chemotherapy, endocrine therapy, and molecular targeted treatments. Therapeutic resistance and tumor recurrence or metastasis develop with the ongoing treatments. Conducive treatment strategies are thus required. Chimeric antigen receptor (CAR)-modified T-cell therapy has progressed as a part of tumor immunotherapy. However, CAR-T treatment has not been effective in solid tumors because of tumor microenvironment complexity, inhibitory effects of extracellular matrix, and lacking ideal tumor antigens. Herein, the prospects of CAR-T cell therapy for metastatic breast cancer are discussed, and the targets for CAR-T therapy in breast cancer (HER-2, C-MET, MSLN, CEA, MUC1, ROR1, EGFR) at clinical level are reviewed. Moreover, solutions are proposed for the challenges of breast cancer CAR-T therapy regarding off -target effects, heterogeneous antigen expression by tumor cells and immunosuppressive tumor microenviron-ment. Ideas for improving the therapeutics of CAR-T cell therapy in metastatic breast cancer are suggested.

Automated summary

Breast cancer is the most common cancer in women, and a significant percentage of patients experience invasion or metastasis despite surgical resection. Current treatments, such as chemotherapy and targeted therapy, are not effective in all cases. CAR-T cell therapy has shown promise in tumor immunotherapy, but its effectiveness in solid tumors, including breast cancer, is limited due to various factors. This article discusses the prospects and challenges of CAR-T cell therapy in metastatic breast cancer and reviews the clinical targets for this therapy. Solutions and ideas for improving the efficacy of CAR-T cell therapy in breast cancer are also proposed.