Immunological and Antitumor Effects of IL-23 as a Cancer Vaccine Adjuvant

W.W. Overwijk, K.E. de Visser, F.H. Tirion, L.A. de Jong, T.W. Pols, Y.U. van der Velden, J.G. van den Boorn, A.M. Keller, W.A. Buurman, M.R. Theoret, B. Blom, N.P. Restifo, A.M. Kruisbeek, R.A. Kastelein, J.B. Haanen

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The promising, but modest, clinical results of many human cancer vaccines indicate a need for vaccine adjuvants that can increase both the quantity and the quality of vaccine-induced, tumor-specific T cells. In this study we tested the immunological and antitumor effects of the proinflammatory cytokine, IL-23, in gp100 peptide vaccine therapy of established murine melanoma. Neither systemic nor local IL-23 alone had any impact on tumor growth or tumor-specific T cell numbers. Upon specific vaccination, however, systemic IL-23 greatly increased the relative and absolute numbers of vaccine-induced CD8(+) T cells and enhanced their effector function at the tumor site. Although IL-23 specifically increased IFN-gamma production by tumor-specific T cells, IFN-gamma itself was not a primary mediator of the vaccine adjuvant effect. The IL-23-induced antitumor effect and accompanying reversible weight loss were both partially mediated by TNF-alpha. In contrast, local expression of IL-23 at the tumor site maintained antitumor activity in the absence of weight loss. Under these conditions, it was also clear that enhanced effector function of vaccine-induced CD8(+) T cells, rather than increased T cell number, is a primary mechanism underlying the antitumor effect of IL-23. Collectively, these results suggest that IL-23 is a potent vaccine adjuvant for the induction of therapeutic, tumor-specific CD8(+) T cell responses
Original languageEnglish
Pages (from-to)5213-5222
JournalJournal of Immunology
Issue number9
Publication statusPublished - 1 Jan 2006

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