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 α-tocopheryl succinate (α-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 α-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 α-TOS alone (mean tumor volume of 471 ± 68 mm3 on day 30 post-tumor injection). Additionally, the adjuvant effect of α-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 α-TOS + DCs. Analysis of purified T lymphocytes from mice treated with α-TOS + DC revealed significantly increased secretion of IFN-γ as compared to T cells from the various control groups. Conclusion: This study demonstrates the potential usefulness of α-tocopheryl succinate, an agent nontoxic to normal cell types, as an adjuvant to augment the effectiveness of DC-based vaccines in treating established tumors. © Springer-Verlag 2004.