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01-07-2004 | Original Article

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

Authors: Lalitha V. Ramanathapuram, James J. Kobie, David Bearss, Claire M. Payne, Katrina T. Trevor, Emmanuel T. Akporiaye

Published in: Cancer Immunology, Immunotherapy | Issue 7/2004

Abstract

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.

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Title: α-Tocopheryl succinate sensitizes established tumors to vaccination with nonmatured dendritic cells
Authors: Lalitha V. Ramanathapuram
James J. Kobie
David Bearss
Claire M. Payne
Katrina T. Trevor
Emmanuel T. Akporiaye
Publication date: 01-07-2004
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 7/2004
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-004-0499-7

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