alpha-Tocopheryl succinate sensitizes established tumors to vaccination with nonmatured dendritic cells.

PURPOSE: Dendritic cells (DCs) 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 against 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. METHODS: In this study we have employed alpha-tocopheryl succinate (alpha-TOS), a nontoxic esterified analogue of vitamin E, as an adjuvant to enhance the effectiveness of DC vaccines in treating established murine Lewis lung (3LL) carcinomas. RESULTS: We demonstrate that locally or systemically administered alpha-TOS in combination with nonmatured DCs injected intratumorally (i.t.) or subcutaneously (s.c.) significantly inhibits the growth of preestablished 10-day tumors (mean tumor volume of 77.5 +/- 17.8 mm3 on day 30 post-tumor injection) as compared to alpha-TOS alone (mean tumor volume of 471 +/- 68 mm3 on day 30 post-tumor injection). Additionally, the adjuvant effect of alpha-TOS was superior to that of cyclophosphamide (CTX). The mean tumor volume on day 28 post-tumor injection in mice treated with CTX+DCs was 611 +/- 94 mm3 as compared to 105 +/- 36 mm3 in mice treated with alpha-TOS+DCs. Analysis of purified T lymphocytes from mice treated with alpha-TOS+DC revealed significantly increased secretion of IFN-gamma as compared to T cells from the various control groups. CONCLUSION: This study demonstrates the potential usefulness of alpha-tocopheryl succinate, an agent nontoxic to normal cell types, as an adjuvant to augment the effectiveness of DC-based vaccines in treating established tumors.