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Mutant herpes simplex virus induced regression of tumors growing in immunocompetent rats (1994)

Kaplitt, Michael G. ; Tjuvajev, Juri G. ; Leib, David A. ; [et al.]

Springer

Journal of neuro-oncology 19 (1994), S. 137-147

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ISSN: 1573-7373

Keywords: HSV ; thymidine kinase ; ribonucleotide reductase ; viral vector ; anti-tumor effect

Source: Springer Online Journal Archives 1860-2000

Topics: Medicine

Notes: Summary Herpes simplex virus (HSV) mutants kill dividing tumor cells but spare non-proliferating, healthy brain tissue and may be useful in developing new treatment strategies for malignant brain tumors. Two HSV mutants, a thymidine kinase deficient virus (TK-) and a ribonucleotide reductase mutant (RR-), killed 7/7 human tumor cell lines in tissue culture. The TK-HSV killed Rat RG2 glioma and W256 carcinoma lines but not the rat C6 glioma in culture. TK-HSV replication (12 pfu/cell) was similar to wild-type HSV (10 pfu/cell) in rapidly dividing W256 cells in tissue culture, but was minimal (〈1 pfu/cell) in serum-starved cells, suggesting that the proliferative activity of tumor cells at the site and time of TK-HSV injection may influence efficacyin vivo. Subcutaneous W256 tumors in male Sprague-Dawley rats were injected with TK-HSV or virus free inoculum. A significant effect of TK-HSV therapy on W256 tumor growth was demonstrated compared to controls (p=0.002). Complete regression was observed in 4/9 experimental tumors, with no recurrence over 6 months. Tumor growth in the remaining 5/9 animals was attenuated during the first 3 to 5 days after treatment, but not beyond 5 days compared to 9 matched control animals; no tumor regression was observed in any of the control animals. These results suggest that HSV mutants are potentially useful as novel therapeutic agents in the treatment of tumors in immunocompetent subjects.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF01306455

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Gene delivery to neurons: Is herpes simplex virus the right tool for the job? (1993)

Leib, David A. ; Olivo, Paul D.

New York, NY : Wiley-Blackwell

BioEssays 15 (1993), S. 547-554

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ISSN: 0265-9247

Keywords: Life and Medical Sciences ; Cell & Developmental Biology

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Biology , Medicine

Notes: Herpes simplex virus (HSV)-derived vectors are currently being developed for the introduction of foreign DNA into neurons. HSV vectors can facilitate a range of molecular studies on postmitotic neurons and may ultimately be used for somatic cell gene therapy for certain neurologic diseases. In this article, the salient features of the pathogenesis and molecular biology of HSV relevant to its use as a vector are described, along with an overview of the methods used to derive these vectors. The accomplishments which have been made to date using the HSV vector system are discussed, with emphasis on the issues of this technology which remain to be addressed. HSV has the potential to be a most useful tool for neuronal cell transgenesis and it is likely that important neurobiological questions will be answered using this vector system.

Additional Material: 2 Ill.