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


CONCLUSIONS
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.
Department of Microbiology and Immunology, University of Arizona, 1501 N. Campbell Avenue, AZ 85724, Tucson, USA.
Lalitha V
LV
Ramanathapuram
James J
JJ
Kobie
David
D
Bearss
Claire M
CM
Payne
Katrina T
KT
Trevor
Emmanuel T
ET
Akporiaye
D000276:Adjuvants, Immunologic; D000818:Animals; D017209:Apoptosis; D019496:Cancer Vaccines / Q000276:immunology*; D018827:Carcinoma, Lewis Lung / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D007371:Interferon-gamma / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology / Q000628:therapy*; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D024505:Tocopherols; D014611:Vaccination; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D014810:Vitamin E; D007371:Interferon-gamma; D024505:Tocopherols