Adenovirus Encoding Human Platelet-Derived Growth Factor-B Delivered in Collagen Exhibits Safety, Biodistribution, and Immunogenicity Profiles Favorable for Clinical Use
2004; Elsevier BV; Volume: 9; Issue: 5 Linguagem: Inglês
10.1016/j.ymthe.2004.02.018
ISSN1525-0024
AutoresDanling Gu, Thanh Nguyen, Ana María González-Castro, Marie A. Printz, Glenn F. Pierce, Barbara A. Sosnowski, M. Laurie Phillips, Lois A. Chandler,
Tópico(s)Tendon Structure and Treatment
ResumoWe have developed a therapeutic approach to wound repair involving immobilization of gene transfer vectors within biocompatible matrices (gene-activated matrix, or GAM). The matrix also serves as a scaffold for cellular in-growth and subsequent gene uptake and expression. An adenoviral vector encoding human platelet-derived growth factor-B delivered in collagen (AdPDGF-B/GAM) has demonstrated efficacy in models of wound repair. The safety, biodistribution, and immunogenicity profiles of AdPDGF-B/GAM were examined using a rabbit dermal wound model. Four weekly doses at 1 x 10(10) and 1 x 10(11) viral particles/cm2 of wound surface stimulated dose-related increases in granulation tissue formation and cell proliferation. In situ hybridization and immunostaining demonstrated concordant expression of human PDGF-B mRNA and protein. No treatment-related changes in hematology, serum chemistry, or histopathology were observed. Although AdPDGF-B DNA and PDGF-B mRNA were detected in wounds and axillary lymph nodes of treated animals, no AdPDGF-B was detected in blood or other organs. No immunologic responses against collagen were observed; however, as expected, IgG responses to AdPDGF-B and human PDGF-BB protein were detected. In adenovirus-preimmunized rats, attenuation of the wound healing response was modest (approximately 16%). Collectively, these observations indicate that repeat doses of AdPDGF-B/GAM are well tolerated and lead to robust, localized tissue repair.
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