Vitamin E Succinate as an Adjuvant for Dendritic Cell Based Vaccines
Annual summary rept. 1 Jul 2003-30 Jun 2004
ARIZONA UNIV TUCSON
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Dendritic cells DC are considered potential candidates for cancer immunotherapy due to their ability to process and present antigens to T cells and stimulate immune responses. However, DC-based vaccines have exhibited minimal effectiveness in abrogating established tumors in mice and human cancer patients. The use of appropriate adjuvants can enhance the efficacy of Dc-based cancer vaccines in treating established tumors. In this study we have employed Vitamin E succinate also known as alpha-tocopheryl succinate alpha-TOS, a non-toxic esterified analogue of Vitamin E, as an adjuvant to enhance the effectiveness of DC vaccines in treating established murine mammary 4T1 carcinomas. The hypothesis to be tested is that alpha-TOS chemotherapy will enhance the efficacy of DC vaccines in treating established tumors and also induce long-term anti-tumor immunity. The rationale for the hypothesis is based on documented evidence that DCs are capable of ingesting apoptotic tumor cells and presenting tumor associated antigens to T lymphocytes to elicit tumor-specific immune responses. The specific aims are to 1 study the effect of alpha-TOS on tumor cells in vitro, 2 determine the efficacy of alpha-TOS and DC combination therapy in treating pre-established murine mammary tumors in vivo, 3 identifyde the immune mechanism involved in mediating the anti-tumor response.
- Medicine and Medical Research