Cancer Immunity 2:4 (2002)

Immunization against a dominant tumor antigen abrogates immunogenicity of the tumor

Amira Makki¹, Gunnar Weidt¹, Nathalie E. Blachere^1*, Leo Lefrançois², and Pramod K. Srivastava^1,2

¹Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, Farmington, CT
²Division of Immunology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT
^*Present address: Rockefeller University, 1230 York Avenue, New York, NY 10021

Keywords: mice, immunization, cytotoxic T Lymphocytes, immunodominant epitopes, tumor immunity

Abstract

To study the role of subdominant epitopes in tumor rejection we have used EL4 tumor cells and their ovalbumin (OVA)-transfected counterpart E.G7. Immunization of mice with irradiated EL4 cells conferred protection against challenge with EL4 and E.G7. Surprisingly, immunization with irradiated E.G7 cells did not protect against a subsequent challenge with EL4 or E.G7. Growth of E.G7 tumors in E.G7 immunized mice was not due to loss of expression of OVA or MHC I by the tumor cells in vivo. Adoptive transfer of OVA-specific transgenic T cells, immunization of mice with native or heat-denatured OVA or infection with a recombinant virus expressing OVA also failed to induce rejection of E.G7 tumors. Lack of immunogenicity of the OVA-expressing tumor could not be overcome by combination of a CD40 activating antibody with immunization against E.G7 or OVA. Our results suggest that immunization against subdominant epitopes is more effective than vaccination against dominant epitopes.