OBJECTIVE: The 4T1 triple negative breast cancer (TNBC) model resembles many of the hallmarks of advanced TNBC in humans. In this study we investigate if combining a membrane-based immunotherapy with immune checkpoint blockade antibodies in a metastatic tumor model could effectively generate protective immunity. This personalized strategy is applicable to indications such as TNBC that exhibit a high degree of heterogeneity and do not respond to approved cancer therapies.
METHODS: 4T1 tumor tissue was harvested from BALB/c mice and processed to generate tumor membrane vesicles (TMVs). TMVs were then incorporated with GPI-B7-1 and GPI-IL-12 by protein transfer and used for immunization in conjunction with immune checkpoint inhibitors. Survival was assessed using a Kaplan-Meier survival curve and significance determined using a Log-rank test for comparison analysis. Metastasis was assessed by clonogenic assay. Immune response was assessed by IFN-γ ELISPOT. Cell depletion studies were performed with anti-CD4 and anti-CD8 antibodies. Significance was determined using a student’s t test to compare metastasis and immune responses.
RESULTS: TMV-based immunotherapy in combination with anti-CTLA-4 antibody significantly improved survival, reduced pulmonary metastasis, and increased tumor-specific CD8 T cell responses. Interestingly, either treatment alone failed to have a significant impact on survival, metastasis, or immune response.
CONCLUSIONS: These results strongly suggest that a TMV-based immunotherapy in combination with anti-CTLA-4 antibody generates effective antitumor immunity. Such a combinatorial approach could potentially translate into an effective treatment for patients with metastatic TNBC.
