HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Google Scholar Articles by Sikora, A. G. Articles by Overwijk, W. W. PubMed PubMed Citation Articles by Sikora, A. G. Articles by Overwijk, W. W.

IFN- Enhances Peptide Vaccine-Induced CD8⁺ T Cell Numbers, Effector Function, and Antitumor Activity¹

Andrew G. Sikora^*,, Nina Jaffarzad^*, Yared Hailemichael^*, Alexander Gelbard^*,, Spencer W. Stonier, Kimberly S. Schluns, Loredana Frasca, Yanyan Lou^*, Chengwen Liu^*, Helen A. Andersson^*, Patrick Hwu^* and Willem W. Overwijk^2,*

^* Department of Melanoma Medical Oncology, Department of Head and Neck Surgery, and Department of Immunology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030; and Department of Head and Neck Surgery, and Bobby Alford Department of Otolaryngology, Baylor College of Medicine, Houston, TX 77030

Type I IFNs, including IFN-, enhance Ag presentation and promote the expansion, survival, and effector function of CD8⁺ CTL during viral infection. Because these are ideal characteristics for a vaccine adjuvant, we examined the efficacy and mechanism of exogenous IFN- as an adjuvant for antimelanoma peptide vaccination. We studied the expansion of pmel-1 transgenic CD8⁺ T cells specific for the gp100 melanocyte differentiation Ag after vaccination of mice with gp100_25–33 peptide in IFA. IFN- synergized with peptide vaccination in a dose-dependent manner by boosting relative and absolute numbers of gp100-specific T cells that suppressed B16 melanoma growth. IFN- dramatically increased the accumulation of gp100-specific, IFN--secreting, CD8⁺ T cells in the tumor through reduced apoptosis and enhanced proliferation of Ag-specific CD8⁺ T cells. IFN- treatment also greatly increased the long-term maintenance of pmel-1 CD8⁺ T cells with an effector memory phenotype, a process that required expression of IFN- receptor on the T cells and IL-15 in the host. These results demonstrate the efficacy of IFN- as an adjuvant for peptide vaccination, give insight into its mechanism of action, and provide a rationale for clinical trials in which vaccination is combined with standard-of-care IFN- therapy for melanoma.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was partially supported by VENI Grant 916.046.014 from the Netherlands Organization for Scientific Research (NWO) to W.W.O., the MDACC SPORE in melanoma P50 CA093459 and by National Institutes of Health Grant AI070910 and the M.D. Anderson Trust Fellowship to K.S. This work was also partially supported by a National Research Service Award Institutional Training Grant T32 DC007367 from NIDCD.

² Address correspondence and reprint requests to Dr. Willem Overwijk, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 0904, Houston, TX 77030. E-mail address: woverwijk{at}mdanderson.org

³ Abbreviations used in this paper: pDC, plasmacytoid dendritic cell; HGT, hydrodynamic gene transfer; CM, complete medium; rIFN-, recombinant Universal IFN-; WT, wild type; mDC, myeloid dendritic cell; IFNAR, IFN- receptor.

This article has been cited by other articles:

				C. A. Klebanoff, Z. Yu, L. N. Hwang, D. C. Palmer, L. Gattinoni, and N. P. Restifo Programming tumor-reactive effector memory CD8+ T cells in vitro obviates the requirement for in vivo vaccination Blood, August 27, 2009; 114(9): 1776 - 1783. [Abstract] [Full Text] [PDF]