The antitumor and immunoadjuvant effects of IFN-α in combination with recombinant poxvirus vaccines

Kenneth W. Hance, Connie J. Rogers, David A. Zaharoff, Daniel Canter, Jeffrey Schlom, John W. Greiner

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Purpose: IFN-α is a pleiotropic cytokine possessing immunomodulatory properties that may improve the efficacy of therapeutic cancer vaccines. The aim of this study was to evaluate the effectiveness and compatibility of combining recombinant IFN-a with poxvirus vaccines targeting the human carcinoembryonic antigen (CEA) in murine models of colorectal and pancreatic adenocarcinomas, whereCEA is aself-antigen. Experimental Design: The phenotypic and functional effects of IFN-α were evaluated in the draining inguinal lymph nodes of tumor-free mice. We studied the effect of the site of IFN-α administration (local versus distal) on antigen-specific immune responses to poxvirus vaccination. Mechanistic studies were conducted to assess the efficacy of IFN-α and CEA-directed poxvirus vaccines in tumor-bearing CEA transgenic mice. Results: We identified a dose and schedule of IFN-α that induced a locoregional expansion of the draining inguinal lymph nodes and improved cellular cytotoxicity (natural killer and CD8 +)and antigen presentation. Suppression of the vaccinia virus was avoided by administering IFN-α distal to the site of vaccination. The combination of IFN-α and vaccine inhibited tumor growth, improved survival, and elicited CEA-specific CTL responses in mice with CEA + adenocarcinomas. In mice with pancreatic tumors, IFN-α slowed tumor growth, induced CTL activity, and increased CD8 + tumor-infiltrating lymphocytes. Conclusions: These data suggest that IFN-α can be used as a biological response modifier with antigen-directed poxvirus vaccines to yield significant therapeutic antitumor immune responses. This study provides the rationale and mechanistic insights to support a clinical trial of this immunotherapeutic strategy in patients with CEA-expressing carcinomas.

Original languageEnglish (US)
Pages (from-to)2387-2396
Number of pages10
JournalClinical Cancer Research
Volume15
Issue number7
DOIs
StatePublished - Apr 1 2009

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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