Abstract Details

Presented By:Frandsen, Jordan
Affiliated with:University of Utah, Bioengineering
Authors:Khaled Greish (1-2), Jordan Frandsen(2-3), Stephanie Scharff (4), Joshua Gustafson (2-3), Hamid Ghandehari (1-3)
From:1Department of Pharmaceutics and Pharmaceutical Chemistry, 2Utah Center for Nanomedicine, Nano Institute of Utah, and 3Department of Bioengineering, University of Utah, Salt Lake City, UT, USA. 4Philipps University of Marburg, Marburg, Germany
Title
Silk-elastinlike protein polymers improve the efficacy of gene therapy of head and neck tumors
Abstract

Objective: To improve intratumoral delivery of adenoviruses encoding for thymidine kinase (Ad-TK) using recombinant silk-elastinlike protein polymer (SELP) matrices.

Methods: Recombinant liquid SELP analogues with similar silk to elastin repeat ratios but different lengths, namely SELP-47K with 4 silklike and 8 elastinlike units per block and SELP-815K with twice as many silk and elastin units per block, were mixed with Ad-TK containing a luciferase gene. Virus-SELP mixtures were directly injected into subcutaneous xenograft tumors of human head and neck carcinomas in nude mice where they formed hydrogels at body temperature. The prodrug ganciclovir was administered at 25 mg/kg body weight to the mice daily for 10 days. Anticancer efficacy was measured by tumor volume reduction. Duration and localization of gene expression were evaluated by a bioluminescent imaging system 30 minutes after injection of luciferin twice per week.

Results: SELP-815K at 4 wt% efficiently improved the duration and extent of transfection of Ad-TK in head and neck tumors for up to 5 weeks with no detectable spread to the liver. About a five-fold greater reduction in tumor volume was obtained with matrix-mediated delivery compared to intratumoral injection of adenoviruses in saline.

Conclusions: With systematic control over the structure of SELPs using recombinant techniques it is possible to design matrices that maximize the delivery of adenoviral gene vectors to head and neck tumors and minimize dissemination to nontarget sites.

Acknowledgements: This research was supported by the National Institutes of Health (R01-CA107621 ) and the Utah Science Technology and Research (USTAR) Initiative.