Vitamin E Succinate as an Adjuvant for Dendritic Cell-Based Vaccines

摘要

Dendritic cells (DC) are considered attractive candidates for cancer immunotherapy due to their ability to process and present antigens and stimulate the immune system. However DC have not been as effective in treating established disease in animal models. This provides the rationale for combining DC vaccines with a chemotherapeutic drug, which may act as an adjuvant for DC vaccines. Vitamin E succinate or alpha tocopheryl succinate (a-TOS) is a non-toxic, esterified analogue of Vitamin E that has been shown to be selectively toxic to tumor cell lines in vitro as well as inhibit the growth of tumors in animal models in vivo. The objective of this study is to enhance the effectiveness of DC vaccines by using it in combination with the non-toxic, more soluble vesiculated version of the chemotherapeutic agent, Va-TOS to treat pre-established tumors of the highly metastatic murine mammary cancer cell line 4T1. The specific aims are to study the effect of Va-TOS in inducing apoptosis in tumor cells in vitro and in vivo, determine the efficacy of Va-TOS and DC combination therapy in treating a pre-established murine mammary tumors and lung metastasis after resection of primary tumor in a residual disease setting identify the mechanism involved in mediating the anti-tumor response.