Developing an Experimental Protocol for the Use of the Zika Virus as an Immunotherapy for Triple-Negative Breast Cancer
Triple-negative breast cancer (TNBC) tumors are associated with a higher rate of metastasis, a higher risk of recurrence, and a worse prognosis. These tumors are highly complex, aggressive, and lack expression of three receptors: estrogen receptor, progesterone receptor, and human epidermal growth receptor 2. The lack of expression of these three receptors, as well as the disease’s heterogeneity, makes it difficult to treat TNBC, suggesting a need for new therapies. TNBC is considered to be a good candidate for immunotherapy with its higher mutational burden, higher levels of programmed death-ligand 1, and higher levels of tumor-infiltrating lymphocytes in the tumor microenvironment. We hypothesized that the Zika virus, which has recently been studied as a prospective immunotherapy for brain cancer, could be applied to treat TNBC, which frequently results in brain metastases. This project aimed to develop an experimental protocol to best test that hypothesis. First, an experimental design was created to test the immunotherapy in a mice model. Then, experiments were conducted to determine the optimal dosage of cancer cells needed to cause tumor growth in the mammary pads and in the brain, to determine the infectivity of the Zika virus available, and to determine the effectiveness of object detection technology during viral titering. We found that the volume of cells injected resulted in survival times that should be sufficient to allow immune cells to become activated and traffic to the sites of tumor proliferation for targeting and eradication. We also found that the Zika virus we used was lower in infectivity than expected, suggesting a need to further investigate methods to increase infectivity and a need to take this infectivity into consideration when creating a TNBC/Zika vaccine in the future. Finally, we found no significant difference between the plaque counts generated by humans and a MATLAB computer program during viral titering, suggesting that while MATLAB may be able to efficiently count the number of plaques, human intervention is still necessary. All of these preliminary experiments help develop and improve the protocol for a future experiment involving a TNBC/Zika vaccine, bringing researchers a step closer to developing a promising immunotherapy for TNBC.