Replication-competent oncolytic herpes simplex viruses (HSVs) are considered a promising therapeutic approach for treatment of high-grade gliomas (HGGs), which are usually resistant to all the available treatments. We previously demonstrated that R-LM113, a recombinant HSV-1 fully retargeted to the human epidermal growth factor receptor 2 (HER2), is safe and prolongs survival of immunodeficient NOD/SCID mice in an intracranial model of HGG. However, because the treatment is designed to be employed on immunocompetent patients, it is necessary to test whether the host immune system impairs the viral efficacy or triggers a potentially fatal reaction. Here we confirmed the safety of R-LM113 in the immunocompetent mouse strain BALB/c, where it does not trigger encephalitis when intracranially inoculated. Then, we set up a syngeneic HGG model expressing HER2 in adult BALB/c mice and evaluated R-LM113 therapeutic efficacy. We found that R-LM113 leads to a significant improvement in animal survival when administered at the time of tumor inoculation, as well as when injected into an already established tumor. This study suggests that the host immune defenses do not curtail the oncolytic antitumor activity of replication-competent HSV R-LM113, which results effective in counteracting tumor growth.
Reisoli E., Gambini E., Appolloni I., Gatta V., Barilari M., Menotti L., et al. (2012). Efficacy of HER2 retargeted herpes simplex virus as therapy for high-grade glioma in immunocompetent mice. CANCER GENE THERAPY, 19(11), 788-795 [10.1038/cgt.2012.62].
Efficacy of HER2 retargeted herpes simplex virus as therapy for high-grade glioma in immunocompetent mice.
GATTA, VALENTINA;MENOTTI, LAURA;
2012
Abstract
Replication-competent oncolytic herpes simplex viruses (HSVs) are considered a promising therapeutic approach for treatment of high-grade gliomas (HGGs), which are usually resistant to all the available treatments. We previously demonstrated that R-LM113, a recombinant HSV-1 fully retargeted to the human epidermal growth factor receptor 2 (HER2), is safe and prolongs survival of immunodeficient NOD/SCID mice in an intracranial model of HGG. However, because the treatment is designed to be employed on immunocompetent patients, it is necessary to test whether the host immune system impairs the viral efficacy or triggers a potentially fatal reaction. Here we confirmed the safety of R-LM113 in the immunocompetent mouse strain BALB/c, where it does not trigger encephalitis when intracranially inoculated. Then, we set up a syngeneic HGG model expressing HER2 in adult BALB/c mice and evaluated R-LM113 therapeutic efficacy. We found that R-LM113 leads to a significant improvement in animal survival when administered at the time of tumor inoculation, as well as when injected into an already established tumor. This study suggests that the host immune defenses do not curtail the oncolytic antitumor activity of replication-competent HSV R-LM113, which results effective in counteracting tumor growth.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
