Therapy of established tumors in a novel murine model transgenic for human carcinoembryonic antigen and HLA-A2 with a combination of anti-idiotype vaccine and CTL peptides of carcinoembryonic antigen

Asim Saha, Sunil K. Chatterjee, Kenneth A. Foon, Esteban Celis, Malaya Bhattacharya-Chatterjee

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Induction of potent and sustained antitumor immunity depends on the efficient activation of CD8+ and CD4+ T cells. Immunization using dendritic cells loaded with tumor antigens constitute a powerful platform for stimulating cellular immunity. Our previous studies suggested that vaccination with an anti-idiotype antibody 3H1, which mimics a specific epitope of carcinoembryonic antigen (CEA), has the potential to break immune tolerance to CEA and induce anti-CEA antibody as well as CEA-specific CD4+ T-helper responses in colon cancer patients as well as in mice transgenic for human CEA. Here, we have combined the anti-idiotype 3H1 with the CTL peptides of CEA to augment both T-helper and CTL responses in a clinically relevant mouse model, which is transgenic for both CEA and HLA-A2. We have evaluated the potential of two different HLA-A2-restricted epitopes of CEA pulsed into dendritic cells in a therapeutic setting. The overall immune responses and survival were enhanced in groups of mice immunized with agonist peptide for CEA691 (YMIGMLVGV)-pulsed dendritic cells or CAP1-6D (YLSGADLNL, agonist peptide for CAP-1)-pulsed dendritic cells. Mice immunized with peptide-pulsed dendritic cells along with 3H1-pulsed dendritic cells resulted in significant increase in survival compared with mice immunized with peptide-pulsed dendritic cells alone (P < 0.02). IFN-γ ELISPOT and 51Cr-release assays showed that HLA-A2-restricted, CEA-specific CTL responses were augmented by combined dendritic cell vaccinations. The combined vaccination strategy resulted in increased antigen-specific proliferation of splenocytes and secretion of Th1 cytokines by CD4+ T cells that correlated with increased survival. These results suggest the potential use of this vaccination strategy for future clinical applications.

Original languageEnglish (US)
Pages (from-to)2881-2892
Number of pages12
JournalCancer Research
Volume67
Issue number6
DOIs
StatePublished - Mar 15 2007
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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