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.
Makki
Amira
A
Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, Farmington, CT 06030-1601, USA.
Weidt
Gunnar
G
Blachere
Nathalie E
NE
Lefrançois
Leo
L
Srivastava
Pramod K
PK
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