Purpose There is currently no curative treatment for patients diagnosed with triple-negative breast cancer brain metastases (TNBC-BM). CAR T cells hold potential for curative treatment given they retain the cytolytic activity of a T cell combined with the specificity of an antibody. In this proposal we evaluated the potential of EGFR re-directed CAR T cells as a therapeutic treatment against TNBC cells in vitro and in vivo . Methods We leveraged a TNBC-BM tissue microarray and a large panel of TNBC cell lines and identified elevated epidermal growth factor receptor (EGFR) expression. Next, we designed a second-generation antiEGFR CAR T construct incorporating a clinically relevant mAb806 tumor specific single-chain variable fragment (scFv) and intracellular 4-1BB costimulatory domain and CD3ζ using a lentivirus system and evaluated in vitro and in vivo anti-tumor activity. Results We demonstrate EGFR is enriched in TNBC-BM patient tissue after neurosurgical resection, with six of 13 brain metastases demonstrating both membranous and cytoplasmic EGFR. Eleven of 13 TNBC cell lines have EGFR surface expression ≥85% by flow cytometry. EGFR806 CAR T treated mice effectively eradicated TNBC-BM and enhanced mouse survival (log rank p<0.004). Conclusion Our results demonstrates anti-tumor activity of EGFR CAR T cells against TNBC cells in vitro and in vivo . Given EGFR CAR T cells are currently undergoing clinical trials in primary brain tumor patients without obvious toxicity, our results are immediately actionable against the TNBC-BM patient population.
Metastatic breast cancer has a poor prognosis, and many patients practice yoga or use other complementary and alternative medicine (CAM) in their healthcare. CAM has risks and benefits, and it will be useful to understand the role of CAM integrated with conventional treatments such as chemotherapy and radiation. Patients with metastatic cancer may respond differently to CAM than those without metastases, and less literature has addressed disease progression in this regard. This short review will attempt to address CAM usage in patients with breast cancer, focused on metastatic disease. The review will address some geographical and cultural differences in CAM usage, benefits of yoga for this patient population to improve quality of life, and highlight study limitations and implementation.
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