Cutting edge: restoration of the ability to generate CTL in mice immune to adenovirus by delivery of virus in a collagen-based matrix.
Viruses are commonly used for the delivery of genes coding for tumor-associated Ags to elicit tumor-specific immune responses. The success of viral vectors has been limited in preclinical and clinical trials in part because of antiviral immunity. We investigated the ability of a collagen-based matrix (Gelfoam; Pharmacia and Upjohn, Kalamazoo, MI) to improve CTL activation by recombinant adenovirus. The data show that coinjection of Gelfoam with type 5 adenovirus recombinant for prostate-specific Ag (Ad5-PSA) enhanced CTL activation. Ad5-PSA priming in Gelfoam also abrogated the inhibitory effects of adenoviral immunity on CTL activation in mice naive to PSA but immune to adenovirus. Finally, Gelfoam enhanced immunization in a self-Ag model using type 5 adenovirus recombinant for membrane-bound OVA (Ad5-mOVA) in rat insulin promoter (RIP)-mOVA-transgenic mice. Thus, Gelfoam enhances CTL activation by recombinant viral vectors in a setting where preformed Ab to the virus is present and also in a tolerant self-Ag model.
Siemens
D R
DR
Departments of. Urology and Microbiology, Prostate Cancer Research Group, Immunology Program, Veterans Administration Medical Center, and Cancer Center, University of Iowa, Iowa City, IA 52242, USA.
Elzey
B D
BD
Lubaroff
D M
DM
Bohlken
C
C
Jensen
R J
RJ
Swanson
A K
AK
Ratliff
T L
TL
D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000235:genetics; D000818:Animals; D002460:Cell Line; D003094:Collagen / Q000008:administration & dosage* / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D005781:Gelatin Sponge, Absorbable / Q000008:administration & dosage*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D007115:Immunization Schedule; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D017430:Prostate-Specific Antigen / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D051381:Rats; D013552:Swine; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D003094:Collagen; D017430:Prostate-Specific Antigen