DEVELOPMENT OF A WEARABLE, NON-INVASIVE, TREATMENT DEVICE FOR METASTATIC TRIPLE-NEGATIVE BREAST CANCER (TNBC)

PROJECT SUMMARY/ABSTRACT Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is highly invasive, has limited treatment options, and is prone to recurrence and metastasis. The standard of care for TNBC patients involves neoadjuvant chemotherapy, followed by surgery and radiotherapy. Even with recent advances in immuno-oncological (I-O) treatments, the 5-year survival rate for metastatic TNBC is only 12%. Moreover, only some (~20% of TNBC patients) are eligible for chemo-immunotherapy combination treatment so that a significant patient remaining population will not benefit from current treatments. Therefore, novel effective therapeutic approaches must be developed that complement standard treatments for TNBC and enhance immune responses. To meet this urgent clinical need, we are developing non-pharmacological, wearable, non-invasive, commercially viable medical devices for treating metastatic TNBC. Using induced electric field (iEF) technology with electromagnetic fields of intermediate frequency (< 500 kHz) and low intensity (µV/cm–mV/cm), we have already shown in a preclinical TNBC model in immunocompetent mice that iEF treatment results in a significant decrease in distant metastases to the lungs, primary tumor burden, infiltration of pro-metastatic tumor associated M2-like macrophages, and increased infiltration of activated cytotoxic T cells in the primary tumor microenvironment (TME). This novel iEF therapy elicits potent beneficial and selective biological response by modifying endogenous electric fields (and potential differences) that exist both at the tissue and cellular levels, by introducing exogenous voltages and electric fields that hinder tumor growth and metastasis to the lungs. Both our in vitro and in vivo data support our hypothesis, and the overall goal of this application is to transition our promising results closer yet to the clinic by combining iEF treatment in mouse models, with standard of care chemotherapy in advanced TNBC. We will accomplish this goal by (1) determining and establishing the safety profile of iEF therapy, assessing any adverse effects of iEF therapy in wild-type immunocompetent mice, identifying any observable effects on standard analytes from blood analysis, and (2) determining the ability of iEF therapy combined with standard of care chemotherapeutic agents in established mouse models that recapitulate breast cancer tumor growth, progression, and pulmonary metastasis. We will determine in vivo the efficacy of standalone IEF therapy in decreasing tumor growth and pulmonary metastasis, and then assess the efficacy of combining iEF treatment with standard of care chemo-monotherapies (paclitaxel, capecitabine) in shrinking the primary tumor and preventing pulmonary metastasis. Collectively, this work has the potential for saving the lives of patients with metastatic TNBC who are not responsive to current standard of care, and will contribute to lessening the morbidity of current treatments by potentially lowering the required dose of chemotherapeutic agents.