A long-term memory obtained by genetic immunization results in full protection from a mammary adenocarcinoma expressing an EBV gene.
We have tested the capability of a plasmid DNA (pDNA) expressing the EBV nuclear Ag-4 (EBNA-4) to evoke a T cell response-associated protective immune response against a tumor expressing this gene. We have found that ACA mice immunized with EBNA-4-expressing plasmid were partially protected against syngeneic mammary carcinoma line (S6C) expressing EBNA-4 (S6C-E4). This protection was enhanced by coimmunizing mice with EBNA-4- and GM-CSF-expressing plasmids, and a full protection was achieved by coimmunizing mice with EBNA-4- and IFN-gamma-expressing plasmids. Furthermore, mice that have rejected the EBNA-4-positive tumor were also resistant against a subsequent challenge with the original nontransfected tumor line. We then checked for the ability of pDNA immunization to provide a protective long-term memory response. We indeed found that even after 3 mo from the last immunization, full protection was obtained by this method, as compared with full tumor outgrowth in the control-immunized group. These findings support the concept that a nonviral, pDNA-based vaccination strategy is useful to fully protect from the outgrowth of tumors expressing this EBV gene.
Charo
J
J
Cancer Center Karolinska, Karolinsk Hospital, Stockholm, Sweden. Jehad.Charo@mtc.ki.se
Ciupitu
A M
AM
Le Chevalier De Préville
A
A
Trivedi
P
P
Klein
G
G
Hinkula
J
J
Kiessling
R
R
D000230:Adenocarcinoma / Q000276:immunology* / Q000517:prevention & control; D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D003429:Cross Reactions; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics / Q000276:immunology*; D005260:Female; D005814:Genes, Viral; D007156:Immunologic Memory; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D010957:Plasmids; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology* / Q000627:therapeutic use
D019496:Cancer Vaccines; D019309:Epstein-Barr Virus Nuclear Antigens; D019444:Vaccines, DNA