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Cutting Edge: Restoration of the Ability to Generate CTL in Mice Immune to Adenovirus by Delivery of Virus in a Collagen-Based Matrix

D. Robert Siemens^*, Bennett D. Elzey^*, David M. Lubaroff^*,,,,¶,||, Caitlin Bohlken, Robert J. Jensen^*, Axel Karl Swanson^* and Timothy L. Ratliff^1,*,,,,||

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

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.

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