CTLA-4 blockade in combination with xenogeneic DNA vaccines enhances T-cell responses, tumor immunity and autoimmunity to self antigens in animal and cellular model systems

Polly D. Gregor, Jedd D. Wolchok, Cristina R. Ferrone, Heidi Buchinshky, Jose A. Guevara-Patiño, Miguel Angel Perales, Fariborz Mortazavi, Dean Bacich, Warren Heston, Jean Baptiste Latouche, Michel Sadelain, James P. Allison, Howard I. Scher, Alan N. Houghton

Research output: Contribution to journalArticle

105 Scopus citations

Abstract

Xenogeneic DNA vaccination can elicit tumor immunity through T cell and antibody-dependent effector mechanisms. Blockade of CTLA-4 engagement with B7 expressed on APCs has been shown to enhance T cell-dependent immunity. We investigated whether CTLA-4 blockade could increase T-cell responses and tumor immunity elicited by DNA vaccines. CTLA-4 blockade enhanced B16 tumor rejection in mice immunized against the melanoma differentiation antigens tyrosinase-related protein 2 and gp100, and this effect was stronger when anti-CTLA-4 was administered with booster vaccinations. CTLA-4 blockade also increased the T-cell responses to prostate-specific membrane antigen (PSMA) when given with the second or third vaccination. Based on these pre-clinical studies, we suggest that anti-CTLA-4 should be tested with xenogeneic DNA vaccines against cancer and that special attention should be given to sequence and schedule of administration.

Original languageEnglish (US)
Pages (from-to)1700-1708
Number of pages9
JournalVaccine
Volume22
Issue number13-14
DOIs
StatePublished - Apr 16 2004
Externally publishedYes

Keywords

  • CTLA-4
  • DNA vaccine
  • Tumor immunity

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Fingerprint Dive into the research topics of 'CTLA-4 blockade in combination with xenogeneic DNA vaccines enhances T-cell responses, tumor immunity and autoimmunity to self antigens in animal and cellular model systems'. Together they form a unique fingerprint.

Cite this