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Journal of Virology, April 2002, p. 3564-3569, Vol. 76, No. 7
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.7.3564-3569.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Selective Targeting and Inducible Destruction of Human Cancer Cells by Retroviruses with Envelope Proteins Bearing Short Peptide Ligands

Timothy J. Gollan and Michael R. Green*

Programs in Gene Function and Expression and in Molecular Medicine, Howard Hughes Medical Institute, University of Massachusetts Medical Center, Worcester, Massachusetts 01605

Received 16 August 2001/ Accepted 20 December 2001

In the accompanying study, we show how retroviral tropism can be redirected by insertion of short peptide ligands at multiple locations in envelope. Here we use this approach to selectively target and destroy human cancer cells. Many cancer cells overexpress specific cell surface receptors. We have generated Moloney murine leukemia virus (MLV) envelope derivatives bearing short peptide ligands for gastrin-releasing protein (GRP) and human epidermal growth factor receptors. Pseudotyped viruses containing these chimeric envelope derivatives selectively transduce human cancer cell lines that overexpress the cognate receptor. A retrovirus targeting the GRP receptor can deliver the thymidine kinase gene to human melanoma and breast cancer cells, which are killed by the subsequent addition of ganciclovir. Collectively, our results demonstrate that short peptide ligands inserted at appropriate locations in MLV envelope can selectively target retroviruses to human cancer cells and deliver a therapeutically relevant gene.

* Corresponding author. Mailing address: Program in Gene Function and Expression, University of Massachusetts Medical School, Lazare Research Building, 364 Plantation St., Worcester, MA 01605. Phone: (508) 856-5331. Fax: (508) 856-5473. E-mail: michael.green{at}umassmed.edu.

Journal of Virology, April 2002, p. 3564-3569, Vol. 76, No. 7
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.7.3564-3569.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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