A tritherapy combination of inactivated allogeneic leukocytes infusion and cell vaccine with cyclophosphamide in a sequential regimen enhances antitumor immunity.

BACKGROUND: Tumor-induced immunosuppression can impede tumor-specific immune responses and limit the effects of cancer immunotherapy. The aim of this study was to investigate the possible effects of sequential chemoimmunotherapeutic strategies to enhance antitumor immune responses.

METHODS: Using the E7-expressing tumor TC-1 as the tumor model, the treatment groups were divided into the following groups: (1) inactivated allogeneic leukocyte infusion (ALI), (2) ALI + MMC-inactivated TC-1 cell vaccine, and (3) ALI + MMC-inactivated TC-1 cell vaccine + cyclophosphamide (CTX).

RESULTS: In our study, we demonstrated that treatment with immune-modulating doses of CTX results in a beneficial tumor microenvironment with the suppression of Tregs. ALI has a limited therapeutic effect, as does the MMC-inactivated TC-1 cell vaccine. Our results showed that CTX preconditioning and persistent ALI treatment along with the MMC-inactivated TC-1 cell vaccine resulted in significant inhibition of tumor growth and extended survival.

CONCLUSION: Our study illustrated the effects of immune-modulating doses of a sequential chemoimmunotherapeutic strategy targeting the tumor and its microenvironment. The results suggest potential clinical effects for the immunotherapy of HPV-associated malignancies.