Optimized peptide vaccines eliciting extensive CD8 T-cell responses with therapeutic antitumor effects

Hyun Il Cho, Esteban Celis

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

A major challenge for developing effective therapeutic vaccines against cancer is overcoming immunologic tolerance to tumor-associated antigens that are expressed on both malignant cells and normal tissues. Herein, we describe a novel vaccination approach, TriVax, that uses synthetic peptides representing CD8 T-cell epitopes, Toll-like receptor agonists that function as potent immunologic adjuvants and costimulatory anti-CD40 antibodies to generate large numbers of high-avidity antigen-reactive T cells capable of recognizing and killing tumor cells. Our results show that TriVax induced huge numbers of long-lasting antigen-specific CD8 T cells that displayed significant antitumor effects in vivo. The administration of a TriVax formulation containing a CD8 T-cell epitope derived from a melanosomal antigen (Trp2180-188) elicited antigen-specific CD8 T cells that induced systemic autoimmunity (vitiligo). More important, TriVax immunization was effective in eliciting potent protective antitumor immunity as well as remarkable therapeutic effects against established B16 melanoma. This therapeutic effect was mediated by CD8 T cells via perforin-mediated lysis and required the participation of type-I IFN but not IFNγ. These results suggest that similar strategies would be applicable for the design of effective vaccination for conducting clinical studies in cancer patients.

Original languageEnglish (US)
Pages (from-to)9012-9019
Number of pages8
JournalCancer Research
Volume69
Issue number23
DOIs
StatePublished - Dec 1 2009

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Subunit Vaccines
Therapeutic Uses
CD8 Antigens
T-Lymphocytes
T-Lymphocyte Epitopes
Vaccination
Antigens
Immunologic Adjuvants
Perforin
Vitiligo
Experimental Melanomas
Cancer Vaccines
Toll-Like Receptors
Neoplasm Antigens
Autoimmunity
Anti-Idiotypic Antibodies
Immunity
Immunization
Neoplasms
Peptides

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Optimized peptide vaccines eliciting extensive CD8 T-cell responses with therapeutic antitumor effects. / Cho, Hyun Il; Celis, Esteban.

In: Cancer Research, Vol. 69, No. 23, 01.12.2009, p. 9012-9019.

Research output: Contribution to journalArticle

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