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 matri...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2001-01, Vol.166 (2), p.731-735
Main Authors: Siemens, D. Robert, Elzey, Bennett D, Lubaroff, David M, Bohlken, Caitlin, Jensen, Robert J, Swanson, Axel Karl, Ratliff, Timothy L
Format: Article
Language:English
Subjects:
Adenoviruses, Human - genetics
Adenoviruses, Human - immunology
Adjuvants, Immunologic - administration & dosage
Adjuvants, Immunologic - genetics
Animals
Cell Line
Collagen - administration & dosage
Collagen - immunology
Cytotoxicity, Immunologic - genetics
Gelatin Sponge, Absorbable - administration & dosage
Genetic Vectors - administration & dosage
Genetic Vectors - immunology
Humans
Immunization Schedule
Lymphocyte Activation - genetics
Mice
Mice, Inbred BALB C
Mice, Inbred DBA
Mice, Transgenic
Prostate-Specific Antigen - administration & dosage
Prostate-Specific Antigen - biosynthesis
Prostate-Specific Antigen - genetics
Prostate-Specific Antigen - immunology
Rats
Swine
T-Lymphocytes, Cytotoxic - immunology
T-Lymphocytes, Cytotoxic - virology
Tumor Cells, Cultured
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.166.2.731