Efficient gene transfer to human squamous cell carcinomas by the herpes simplex virus type 1 amplicon vector - 09/09/11

Doi : 10.1016/S0002-9610(98)00231-1

John F. Carew, MD ^a,⁎, Howard Federoff, MD, PhD ^c, Marc Halterman, MD ^d, Dennis H. Kraus, MD ^a, Howard Savage, PhD ^a, Peter G. Sacks, PhD ^a, Stimson P. Schantz, MD ^a, Jatin P. Shah, MD ^a, Yuman Fong, MD ^b
^a Departments of Head and Neck Surgery (JFC, DHK, HS, PGS, SPS, JPS) Memorial Sloan Kettering Cancer Center, New York, New York, USA
^b Department of Surgery (YF), Memorial Sloan Kettering Cancer Center, New York, New York, USA
^c Departments of Neurology, Medicine, and Neuroscience (HF), University of Rochester Medical Center, Rochester, New York, USA
^d Departments of Neurology and Medicine (MH), University of Rochester Medical Center, Rochester, New York, USA

^*Requests for reprints should be addressed to John F. Carew, MD, Department of Head and Neck Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021

Abstract

Background: This study evaluates the efficiency of herpes simplex virus (HSV) mediated gene transfer in human squamous cell carcinoma (SCC) cell lines in vitro and in vivo when delivered by selective intra-arterial perfusion.

Methods: Human head and neck SCC were exposed to HSV-LacZ and HSV–interleukin-2 (IL-2) and gene transfer and expression assessed by X-gal staining and enzyme-linked immunosorbent assay, respectively. Hamster cheek pouch tumors were perfused with HSV-LacZ or HSV–IL-2, by microcannulating the external carotid artery, and gene transfer determined.

Results: A ratio of 5 viral particles per tumor cell achieved gene transfer rates exceeding 50%. Interleukin-2 levels of 287 ± 17 to 424 ± 8.4 ng per million cells were achieved at a ratio of 2 viral particles per tumor cell. Selective intra-arterial perfusion of the HSV–IL-2 vector yielded IL-2 levels of 45.8 ± 17.0 pg per g tumor.

Conclusions: HSV amplicon vectors are efficient vehicles for gene transfer in vitro in human head and neck SCC cell lines and in vivo when introduced by selective intra-arterial perfusion.

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Plan

Materials and methods

Cell culture

HSV amplicon vectors

In vitro X-gal staining

In vitro IL-2 production

Selective intra-arterial perfusion of oral cavity tumor

Statistical analysis

Results

In vitro X-gal staining

In vitro IL-2 production

Selective intraarterial perfusion of oral cavity tumor

Comments

This study was funded by the Society of Head and Neck Surgery Research Grant (JFC), National Cancer Institute-T32 CA 09685 (JFC), and grants CA76416 (YF) and CA 72632 (YF) from the National Institutes of Health.

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Vol 176 - N° 5

P. 404-408 - novembre 1998 Retour au numéro

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Efficient gene transfer to human squamous cell carcinomas by the herpes simplex virus type 1 amplicon vector - 09/09/11

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