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

Vaccine. 2004 Apr 16;22(13-14):1700-8. doi: 10.1016/j.vaccine.2003.10.048.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Neoplasm / biosynthesis
  • Antigens, CD
  • Antigens, Differentiation / immunology
  • Antigens, Differentiation / pharmacology*
  • Autoantigens / immunology*
  • Autoimmunity / immunology*
  • CTLA-4 Antigen
  • Cancer Vaccines / immunology*
  • Cell Line, Tumor
  • Flow Cytometry
  • Humans
  • Immunity, Cellular / immunology*
  • Immunization Schedule
  • Immunosuppressive Agents / pharmacology*
  • Male
  • Melanoma, Experimental / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neoplasm Transplantation
  • Neoplasms / immunology*
  • Plasmids / immunology
  • Prostate / immunology
  • T-Lymphocytes / immunology*
  • Vaccines, DNA / immunology


  • Antibodies, Neoplasm
  • Antigens, CD
  • Antigens, Differentiation
  • Autoantigens
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Cancer Vaccines
  • Ctla4 protein, mouse
  • Immunosuppressive Agents
  • Vaccines, DNA