CD4+CD25+ regulatory T-cell-inactivation in combination with adenovirus vaccines enhances T-cell responses and protects mice from tumor challenge.
Cancer vaccines are a promising approach to treating tumors or preventing tumor relapse through induction of an immune response against tumor-associated antigens (TAA). One major obstacle to successful therapy is the immunological tolerance against self-antigens which limits an effective antitumor immune response. As a transient reduction of immunological tolerance may enable more effective vaccination against self-tumor antigens, we explored this hypothesis in a CEA tolerant animal model with an adenovirus expressing CEA vaccine in conjunction with inactivation of CD4(+)CD25(+) regulatory T cells. This vaccination modality resulted in increased CEA-specific CD8(+), CD4(+) T cells and antibody response. The appearance of a CD4(+) T-cell response correlated with a stronger memory response. The combined CD25(+) inactivation and genetic vaccination resulted in significant tumor protection in a metastatic tumor model. Non-invasive tumor visualization showed that not only primary tumors were reduced, but also hepatic metastases. Our results support the viability of this cancer vaccine strategy as an adjuvant treatment to prevent tumor relapse in cancer patients.
Elia
L
L
Department of Molecular and Cellular Biology, IRBM-Merck Research Laboratory, P. Angeletti, Via Pontina Km 30,600, 00040 Pomezia, Rome, Italy.
Aurisicchio
L
L
Facciabene
A
A
Giannetti
P
P
Ciliberto
G
G
La Monica
N
N
Palombo
F
F
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D015704:CD4 Antigens / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000276:immunology; D002460:Cell Line; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D023421:Models, Animal; D013601:T-Lymphocytes / Q000276:immunology*
D015704:CD4 Antigens; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D053645:Interleukin-2 Receptor alpha Subunit