DNA and adenoviral vectors encoding carcinoembryonic antigen fused to immunoenhancing sequences augment antigen-specific immune response and confer tumor protection.
A panel of vectors was constructed to encode carcinoembryonic antigen (CEA) fused at its C-terminal end to various polypeptides, so as to compare their immunogenicity by plasmid DNA immunization and adenovirus injection in wild-type and CEA transgenic (CEA.tg) mice. Fusions between CEA and the minimized domain of tetanus toxin fragment C (CEA-DOM) or the Fc portion of IgG1 (CEA-FcIgG) were identified as highly immunogenic and elicited significant CEA-specific antibody and CD8+ T cell responses. CEA.tg mice were protected from tumor growth on challenge with MC38-CEA tumor cells only when immunized with repeated injections of plasmid pV1J/CEA-DOM followed by Ad/CEA-DOM. Depletion of T-regulatory cells resulted in an increased immune response and antitumor effect with DNA plus adenovirus immunization. In addition, this protective effect was abrogated if the NK, CD4+, or CD8+ cell population from immunized mice was depleted before tumor challenge. Passive transfer studies demonstrated that CD4+ and CD8+ T cells and antibodies contributed to the antitumor effect, thus suggesting that a genetic vaccine based on the use of plasmid DNA and adenoviral vectors encoding CEA fused to immunoenhancing sequences augments CEA-specific immune responses and effectively protects from tumor development.
Facciabene
Andrea
A
Istituto di Ricerche di Biologia Molecolare (IRBM), Pomezia 00040, Italy.
Aurisicchio
Luigi
L
Elia
Leonardo
L
Palombo
Fabio
F
Mennuni
Carmela
C
Ciliberto
Gennaro
G
La Monica
Nicola
N
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001798:Blood Proteins / Q000235:genetics* / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology* / Q000627:therapeutic use; D016207:Cytokines / Q000187:drug effects; D000939:Epitopes / Q000276:immunology; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009369:Neoplasms / Q000276:immunology* / Q000517:prevention & control; D010957:Plasmids / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000187:drug effects; D011993:Recombinant Fusion Proteins; D013745:Tetanus Toxoid / Q000276:immunology; D014162:Transfection
D001798:Blood Proteins; D002272:Carcinoembryonic Antigen; D016207:Cytokines; D000939:Epitopes; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D013745:Tetanus Toxoid; C011850:immunoenhancing factor