Vectors encoding carcinoembryonic antigen fused to the B subunit of heat-labile enterotoxin elicit antigen-specific immune responses and antitumor effects.
Vectors encoding CEA fused to the A (CEA-LTA) or B (CEA-LTB) subunits of the heat-labile enterotoxin were constructed and their immunogenicity was compared. The CEA-LTB fusion was shown to elicit a greater CEA-specific antibody and CD8+ T-cell response. Plasmid DNA and Adenovirus vectors encoding CEA-LTB proved to be immunogenic in CEA transgenic (CEA.tg) mice. CEA.tg mice immunized with repeated injections of plasmid pV1J/CEA-LTB followed by Ad/CEA-LTB were protected from tumor growth, but the adjuvant activity of the LTB protein was lost upon mutation of the LTB sequence. Depletion of T-regulatory cells increased the vaccine antitumor effect. Tumor protection was abrogated if the NK or CD8+ cell population was depleted before tumor challenge. Passive transfer studies demonstrated that CD8+ T cells contribute to the antitumor effect, thus suggesting that a genetic vaccine based on plasmid DNA and adenoviral vectors encoding CEA-LTB augments CEA-specific immune responses and significantly protects from tumor development.
Istituto di Ricerche di Biologia Molecolare, Via Pontina km 30,600, Pomezia 00040, Italy.
Andrea
A
Facciabene
Luigi
L
Aurisicchio
Leonardo
L
Elia
Fabio
F
Palombo
Carmela
C
Mennuni
Gennaro
G
Ciliberto
Nicola
N
La Monica
D000276:Adjuvants, Immunologic / Q000235:genetics*; D000818:Animals; D001427:Bacterial Toxins / Q000235:genetics* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000235:genetics* / Q000276:immunology*; D004768:Enterotoxins / Q000235:genetics* / Q000276:immunology; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000276:immunology; D005260:Female; D005822:Genetic Vectors; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D014614:Vaccines, Synthetic / Q000276:immunology*
D000276:Adjuvants, Immunologic; D001427:Bacterial Toxins; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; C027538:heat-labile enterotoxin, E coli