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文献-comparison of genetically engineered herpes simplex viruses for the treatment of brain tumors in a scid mouse model of human mal.docx

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1412 1412 Medical Sciences: Chambers et al. Proc. Natl. Acad Set USA 92 (1995) Medical Sciences: Chambers Medical Sciences: Chambers et al Proc. Natl Acad ScL USA 92 (1995) 1413 1411 1411 Proc. Natl. Acad. Sci. USA Vol. 92, pp. 1411-1415, February 1995 Medical Sciences Comparison of genetically engineered herpes simplex viruses for the treatment of brain tumors in a scid mouse model of human malignant glioma (oncolytic viruses/gene therapy/tumor cell targeting) Renee Chambers*, G. Yancey Gillespie*, Liliana Soroceanu*, Samita AndreanskyI SUBHENDRA CHATTERJEEt, JOANY CHOU*, BERNARD ROIZMAN*, AND RICHARD J. WHITLEY§^ Departments of * Neurosurgery, ^Pediatrics and Microbiology, and ^Pediatrics, Microbiology and Medicine, University of Alabama at Birmingham, Birmingham, AL 35284; and ^The Maijorie B. Kovler Viral Oncology Laboratories, University of Chicago, Chicago, IL 60637 Contributed by Bernard Roizman, October 7, 1994 ABSTRACT Genetically engineered viruses and viral genes inserted into retroviral vectors are increasingly being considered for experimental therapy of brain tumors. A primary target of these viruses and vectors is human gliomas, the most frequently occurring primary human brain tumor. To investigate the potential of genetically engineered herpes simplex viruses (HSVs) in the therapy of these tumors, we compared the attributes of two viruses, a recombinant from which the yi34.5 gene had been deleted (R3616) and a recombinant in which the yi34.5 gene had been interrupted by a stop codon (R4009). Previous studies have shown that these recombinants were completely devoid of the ability to multiply in the central nervous system of rodents. To pursue these studies，we developed a scid mouse glioma model. Tumor cell response (survival) for 103,104, and 105 implanted MT539MG glioma cells was 38，23，and 15 days, respectively. The results were as follows: (i) both R3616 and R4009 replicate and cause cytol- ysis in diverse glioma cell lines of murine and hu