The Application of Chimeric Antigen Receptor T-cell Immunotherapy in Breast Cancer Therapeutic Strategies: A literature review study of the current knowledge
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AmirAli Moodi Ghalibaf,1,* Nazanin Forghani,2
1. Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
2. Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Introduction: Today Breast cancer has become the most common malignancy among women all over the world. According to the last studies, it was estimated that more than 2.3 million new cases were in 2020. This high prevalence rate of breast cancer made it a highlighted topic in cancer researches. Although different therapeutic methods have been applied against breast cancer up to now, but the Chimeric antigen receptor (CAR) T-cell therapy is novel innovative immunotherapy in which autologous T-cells are genetically modified to express chimeric receptors encoding an antigen-specific single-chain variable fragment and costimulatory molecules. Based on our current developments, CAR T-cell therapy can be used for hematologic malignancies; however, it seems that this effective therapeutic method can potentially be used in solid tumors treatment such as breast cancer. Therefore, in this literature review study, we discussed the last discoveries about CAR T cell therapy in breast cancer treatment.
- Methods: A comprehensive search was conducted in electronic databases Embase, Pubmed, Scopus, and web of science with the keywords “CAR T-cell”, “Breast cancer” and all other related MeSH words since 2010. Original and review studies that were discussed about the application of CAR T cell therapy in breast cancer included for further investigations.
- Results: According to our comprehensive review of the current knowledge, different studies have been developed for targeting HER2 by CAR T-cells. Also, other targets such as cMET, triple-negative breast cancers, mesothelin, CEA, carbonic anhydrase IX (CAIX), FR-α, CD171, GD2, EGFRvIII, fibroblast activation protein (FAP), and vascular endothelial growth factor receptor 2 (VEGF-R2) could be considerable in CAR T-cell therapy. Although CAR T-cell therapy can have incredible therapeutic effects on malignant cell lines specifically, but some concerns are being existed about its toxicity. In detail, some studies indicated CAR T-cell toxicity as its high expansion in targeted cells. Unfortunately, systemic inflammatory response syndrome or cytokine storm, in which significant release of IFN-γ, TNF-α, IL-2, IL-6, and etc occurs, is the other concern about CAR T-cell therapy. It is notable that some studies indicated that the combination of CAR T-cell therapy with other types of cancer therapies such as target therapy can potentially be more effective and better outcomes can be observed in these cases in comparison with a single therapeutic method.
- Conclusion: Despite CAR T-cell is applied for hematologic malignancies treatment, but its potential role in the management and solid cancers therapy is still under study. Further evaluations are needed to investigate the therapeutic or non-therapeutic effects of this type of cancer immunotherapy in solid cancers, especially breast cancer.
- Keywords: Immunotherapy, Breast cancer, CAR T-cell
