An approach to increase efficacy against triple negative breast cancer using an engineered multigenic vaccinia virus combined with CAR T-cell therapy

Triple negative breast cancer (TNBC) is an aggressive subtype with poor prognosis and limited treatment options. Conventional therapies often lead to systemic relapse, and cancer immunotherapy faces challenges such as insufficient immune activation and lack of tumor specificity. To overcome these limitations, we propose a novel strategy using an engineered oncolytic vaccinia virus (VV) combined with chimeric antigen receptor (CAR) T-cell therapy to treat TNBC. This oncolytic virus is designed to increase tumor specificity through the expression of anti-MUC-1 and ANTXR1 and to reprogram the tumor microenvironment (TME) by integrating PD-L1 inhibitor, CCL5, GM-CSF, and IL-2. This is expected to significantly increase recruitment and function of macrophages, NK cells, granulocytes, and T cells within the TNBC TME and to enhance tumor cell lysis. Additionally, the VV is expected to increase CAR T-cell proliferation and their specific targeting of TNBC cells. Our model provides a specific and immunologically potent treatment for TNBC. Future directions include addressing tumor heterogeneity and minimizing antiviral immune responses.