Tumor membrane-based vaccine immunotherapy in combination with anti-CTLA-4 antibody confers protection against immune checkpoint resistant murine triple-negative breast cancer. Issue 12 (1st December 2020)

• Record Type: Journal Article
• Authors: Pack, Christopher D.; Bommireddy, Ramireddy; Munoz, Luis E.; Patel, Jaina M.; Bozeman, Erica N.; Dey, Paulami; Radhakrishnan, Vijayaraghavan; Vartabedian, Vincent F.; Venkat, Kalpana; Ramachandiran, Sampath; Reddy, Shaker J. C.; Selvaraj, Periasamy
• Is Part Of: Human vaccines & immunotherapeutics. Volume 16:Issue 12(2020)
• Page Start: 3184
• Page End: 3193
• Publication Date: 2020-12-01
• Subjects: Cancer vaccine -- immunotherapy -- CTLA-4 -- CD80 -- IL-12 -- protein transfer -- tumor membrane vesicles -- glycosyl phosphatidylinositol anchor; Vaccines -- Periodicals; 615.372
• DOI: 10.1080/21645515.2020.1754691
• Languages: English
• ISSNs: 2164-5515

Abstract

ABSTRACT: Triple-negative breast cancer (TNBC) afflicts women at a younger age than other breast cancers and is associated with a worse clinical outcome. This poor clinical outcome is attributed to a lack of defined targets and patient-to-patient heterogeneity in target antigens and immune responses. To address such heterogeneity, we tested the efficacy of a personalized vaccination approach for the treatment of TNBC using the 4T1 murine TNBC model. We isolated tumor membrane vesicles (TMVs) from homogenized 4T1 tumor tissue and incorporated glycosyl phosphatidylinositol (GPI)-anchored forms of the immunostimulatory B7-1 (CD80) and IL-12 molecules onto these TMVs to make a TMV vaccine. Tumor-bearing mice were then administered with the TMV vaccine either alone or in combination with immune checkpoint inhibitors. We show that TMV-based vaccine immunotherapy in combination with anti-CTLA-4 mAb treatment upregulated immunomodulatory cytokines in the plasma, significantly improved survival, and reduced pulmonary metastasis in mice compared to either therapy alone. The depletion of CD8 + T cells, but not CD4 + T cells, resulted in the loss of efficacy. This suggests that the vaccine acts via tumor-specific CD8 + T cell immunity. These results suggest TMV vaccine immunotherapy as a potential enhancer of immune checkpoint inhibitor therapies for metastatic triple-negative breast cancer.