Potent oncolytic activity of multimutated herpes simplex virus G207 in combination with vincristine against human rhabdomyosarcoma.

Cinatl, Jindrich and Cinatl, Jaroslav and Michaelis, Martin and Kabicková, Hanka and Kotchetkov, Rouslan and Vogel, Jens-Uwe and Doerr, Hans Wilhelm and Klingebiel, Thomas and Driever, Pablo Hernáiz (2003) Potent oncolytic activity of multimutated herpes simplex virus G207 in combination with vincristine against human rhabdomyosarcoma. Cancer Research, 63 (7). pp. 1508-14. ISSN 0008-5472. (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Abstract

Replication restricted oncolytic viruses such as multimutated herpes simplex virus type 1 (HSV-1) G207 represent a novel and attractive approach for cancer therapy, including pediatric solid tumors. Rhabdomyosarcoma is the most common soft-tissue sarcoma of childhood and is often diagnosed already as an advanced disseminated disease. Despite aggressive therapeutic approaches, the prognosis for patients with metastatic rhabdomyosarcoma remains grim. Therefore, there is a need for novel effective drugs with superior safety and efficacy profile. In this study, we showed marked in vitro activity of HSV-1 G207 against embryonal and alveolar rhabdomyosarcoma cells. All human embryonal (KF-RMS-1, RD, and CCA) and alveolar RMS (KFR, Rh28, Rh30, and Rh41) cell lines were highly sensitive to cytotoxic and replicative effects of G207 even at a multiplicity of infection of 0.01, except embryonal Rh1 rhabdomyosarcoma cells, which were efficiently killed only upon multiplicity of infection of 1.0. i.v. G207 treatment of xenotransplanted KFR and KF-RMS-1 tumors in mice led to significant tumor growth inhibition of both tumor entities, whereas intraneoplastic G207 treatment additionally resulted in complete tumor disappearance in 25% of animals. No difference has been found between alveolar and embryonal types of rhabdomyosarcoma. Combination treatment of both cell lines with G207 and vincristine led to strongly enhanced in vitro cytotoxicity without affecting infection efficiency and replication of G207 in KFR as well as in KF-RMS-1 cells. In vivo combination treatment using i.v. G207 and vincristine resulted in complete regression of alveolar rhabdomyosarcoma in five of eight animals and significant growth inhibition of embryonal rhabdomyosarcoma. Taking into consideration the proven safety of G207 in humans, we suggest that G207 alone and in combination with vincristine should be additionally evaluated as a potential agent against human rhabdomyosarcoma.

Item Type: Article
Subjects: Q Science > QR Microbiology > QR355 Virology
R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Martin Michaelis
Date Deposited: 05 Jun 2013 20:12 UTC
Last Modified: 25 Apr 2014 14:06 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/34123 (The current URI for this page, for reference purposes)
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