Substantially improved in vivo radiosensitization of rat glioma with mutant HSV-TK and acyclovir (original) (raw)

Cancer Gene Therapy volume 8, pages 3–8 (2001)Cite this article

Abstract

We recently demonstrated in vitro that a mutant HSV-TK (mutant 75) expressed from an adenovirus (AdCMV-TK75) radiosensitized rat RT2 glioma cells significantly better than wild type HSV-TK (AdCMV-TK) in combination with acyclovir (ACV). To examine whether a similar improvement could also be observed in vivo, we tested these viruses in a syngeneic rat glioma tumor model (RT2/Fischer 344). First, we demonstrate that treatment with AdCMV-TK and ACV significantly radiosensitizes implanted gliomas and roughly doubles the mean survival time to 37 days, compared to 20 days for control animals implanted with Adβgal-transduced cells (P<.02). Second, it was important to first examine the effect of AdCMV-TK75 and ACV on survival without any irradiation. We found that AdCMV-TK75 appeared to sensitize gliomas more efficiently than AdCMV-TK, although this difference was not significant (_P_=.19). Third, and most importantly, in combined HSV-TK, ACV and irradiation experiments, we demonstrate that AdCMV-TK75 is superior over AdCMV-TK and significantly (P<.005) prolonged the survival of treated animals. Our results suggest that AdCMV-TK75 is far more efficient than AdCMV-TK in radiosensitizing rat glioma when administered in combination with ACV. Cancer Gene Therapy (2001) 8, 3–8

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Authors and Affiliations

  1. Department of Radiation Oncology, Massey Cancer Center, Medical College of Virginia, Virginia Commonwealth University, Richmond, 23298-0058, Virginia
    Kristoffer Valerie, William Hawkins, Julie Farnsworth, Rupert Schmidt-Ullrich, Peck-Sun Lin, Cyrus Amir & Jeffrey Feden

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  1. Kristoffer Valerie
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  2. William Hawkins
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  3. Julie Farnsworth
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  4. Rupert Schmidt-Ullrich
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  5. Peck-Sun Lin
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  6. Cyrus Amir
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  7. Jeffrey Feden
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Correspondence toKristoffer Valerie.

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Valerie, K., Hawkins, W., Farnsworth, J. et al. Substantially improved in vivo radiosensitization of rat glioma with mutant HSV-TK and acyclovir.Cancer Gene Ther 8, 3–8 (2001). https://doi.org/10.1038/sj.cgt.7700265

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