This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Reddy, P. S. Articles by Yu, D.-C. Search for Related Content PubMed PubMed Citation Articles by Reddy, P. S. Articles by Yu, D.-C. Related Collections Commentary

Enhanced Gene Transfer and Oncolysis of Head and Neck Cancer and Melanoma Cells by Fiber Chimeric Oncolytic Adenoviruses

Author's Affiliation: Cell Genesys, Inc., South San Francisco, California

Requests for reprints: Shanthi Ganesh, Oncolytic Virus Research, Cell Genesys, Inc., 500 Forbes Boulevard, South San Francisco, CA 94080. Phone: 650-266-2925; E-mail: shanthi.ganesh{at}cellgenesys.com.

Purpose: The purpose of this study was to evaluate a fiber knob replacement strategy to improve infectivity and efficacy of Ad5 fiber chimeric oncolytic viruses for treatment of melanoma and head and neck cancers (HNC).

Experimental Design: Adenoviral receptors and transduction levels were used to determine the level of infectivity of fiber-modified, green fluorescent protein–expressing, replication-deficient viruses in a panel of melanoma and HNC cell lines in vitro. Virus yield and cytotoxicity assays were used to determine the tumor specificity and virus replication-mediated cytotoxicity of the fiber-modified oncolytic viruses in the same panel of melanoma and HNC in vitro. Xenograft tumor models were used to assess the antitumor activity of those fiber-modified chimeric viruses compared with the parental virus.

Results: Marker gene expression following gene transfer of the fiber chimeric vectors in melanoma and HNC cell lines was 10-fold higher than that obtained with parental Ad5 vector. The fiber chimeric oncolytic variants mediated killing of melanoma and HNC cells that was 2- to 576-fold better than with the parental virus. In addition, fiber chimeric variants produced 2- to 7-fold more progeny virus in tumor cells than the parental virus. Moreover, a high multiplicity of infection was needed for the fiber chimeric viruses to produce cytotoxicity in normal cells. A significantly stronger antitumor response and survival advantage were shown in the tested melanoma and HNC xenograft models following i.t. injections.

Conclusions: In vitro and in vivo studies showed the improved transduction, replication, cytotoxicity, antitumor efficacy, and survival advantage in melanoma and HNC tumor models, suggesting a potential use of these oncolytic agents for the treatment of melanoma and HNCs.

Commentary

Advanced Generation Adenoviral Virotherapy Agents Embody Enhanced Potency Based upon CAR-Independent Tropism

J. Michael Mathis, Phoebe L. Stewart, Zheng B. Zhu, and David T. Curiel
Clin. Cancer Res. 2006 12: 2651-2656. [Full Text] [PDF]

This article has been cited by other articles:

				S. Ganesh, M. Gonzalez-Edick, D. Gibbons, M. Van Roey, and K. Jooss Intratumoral Coadministration of Hyaluronidase Enzyme and Oncolytic Adenoviruses Enhances Virus Potency in Metastatic Tumor Models Clin. Cancer Res., June 15, 2008; 14(12): 3933 - 3941. [Abstract] [Full Text] [PDF]

				S. Ganesh, M. Gonzalez Edick, N. Idamakanti, M. Abramova, M. VanRoey, M. Robinson, C.-O. Yun, and K. Jooss Relaxin-Expressing, Fiber Chimeric Oncolytic Adenovirus Prolongs Survival of Tumor-Bearing Mice Cancer Res., May 1, 2007; 67(9): 4399 - 4407. [Abstract] [Full Text] [PDF]

				J. M. Mathis, P. L. Stewart, Z. B. Zhu, and D. T. Curiel Advanced Generation Adenoviral Virotherapy Agents Embody Enhanced Potency Based upon CAR-Independent Tropism. Clin. Cancer Res., May 1, 2006; 12(9): 2651 - 2656. [Full Text] [PDF]