Immunization against a dominant tumor antigen abrogates immunogenicity of the tumor.
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.
Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, Farmington, CT 06030-1601, USA.
Amira
A
Makki
Gunnar
G
Weidt
Nathalie E
NE
Blachere
Leo
L
Lefrançois
Pramod K
PK
Srivastava
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D002455:Cell Division; D000939:Epitopes / Q000276:immunology; D007114:Immunization; D016056:Immunodominant Epitopes / Q000276:immunology*; D016219:Immunotherapy, Adoptive; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D010047:Ovalbumin / Q000276:immunology; D013601:T-Lymphocytes / Q000637:transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured; D019139:Tumor Escape
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D000939:Epitopes; D016056:Immunodominant Epitopes; D010047:Ovalbumin