A genetically engineered adenovirus vector targeted to CD40 mediates transduction of canine dendritic cells and promotes antigen-specific immune responses in vivo.
Targeting viral vectors encoding tumor-associated antigens to dendritic cells (DCs) in vivo is likely to enhance the effectiveness of immunotherapeutic cancer vaccines. We have previously shown that genetic modification of adenovirus (Ad) 5 to incorporate CD40 ligand (CD40L) rather than native fiber allows selective transduction and activation of DCs in vitro. Here, we examine the capacity of this targeted vector to induce immune responses to the tumor antigen CEA in a stringent in vivo canine model. CD40-targeted Ad5 transduced canine DCs via the CD40-CD40L pathway in vitro, and following vaccination of healthy dogs, CD40-targeted Ad5 induced strong anti-CEA cellular and humoral responses. These data validate the canine model for future translational studies and suggest targeting of Ad5 vectors to CD40 for in vivo delivery of tumor antigens to DCs is a feasible approach for successful cancer therapy.
Division of Human Gene Therapy, Department of Medicine, Birmingham, AL 35294, United States.
Erin E
EE
Thacker
Masaharu
M
Nakayama
Bruce F
BF
Smith
R Curtis
RC
Bird
Zhanat
Z
Muminova
Theresa V
TV
Strong
Laura
L
Timares
Nikolay
N
Korokhov
Ann Marie
AM
O'Neill
Tanja D
TD
de Gruijl
Joel N
JN
Glasgow
Kenzaburo
K
Tani
David T
DT
Curiel
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004285:Dogs; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D011994:Recombinant Proteins / Q000276:immunology; D014161:Transduction, Genetic
D000912:Antibodies, Neoplasm; D019013:CD40 Antigens; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D011994:Recombinant Proteins; D023201:CD40 Ligand