Vector prime/protein boost vaccine that overcomes defects acquired during aging and cancer.
We showed that the Ad-sig-TAA/ecdCD40L vaccine induces a tumor suppressive immune response to the hMUC-1 and rH2N tumor-associated self Ags (TAA) and to the Annexin A1 tumor vascular Ag, even in mice in which anergy exists to these Ags. When the TAA/ecdCD40L protein is given s.c. as a boost following the Ad-sig-TAA/ecdCD40L vector, the levels of the TAA-specific CD8 T cells and Abs increase dramatically over that seen with vector alone, in young (2-mo-old) as well as old (18-mo-old) mice. The Abs induced against hMUC-1 react with human breast cancer. This vaccine also induces a 4-fold decrement of negative regulatory CD4CD25FOXP3-T cells in the tumor tissue of 18-mo-old mice. These results suggest that the Ad-sig-TAA/ecdCD40L vector prime-TAA/ecdCD40L protein boost vaccine platform may be valuable in reducing postsurgery recurrence in a variety of epithelial neoplasms.
Tang
Yucheng
Y
Sidney Kimmel Cancer Center, San Diego, CA 92121, USA.
Akbulut
Hakan
H
Maynard
Jonathan
J
Petersen
Line
L
Fang
Xiangming
X
Zhang
Wei-Wei
WW
Xia
Xiaoqin
X
Koziol
James
J
Linton
Phyllis-Jean
PJ
Deisseroth
Albert
A
D000375:Aging; D000818:Animals; D017305:Annexin A1 / Q000276:immunology; D000951:Antigens, Neoplasm / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000628:therapy; D023201:CD40 Ligand; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D051379:Mice; D009375:Neoplasms, Glandular and Epithelial / Q000628:therapy*; D055502:Secondary Prevention; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D017305:Annexin A1; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D023201:CD40 Ligand