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Published on: December 1, 2013
Herpes simplex virus type 1 mutant HF10 oncolytic viral therapy for bladder cancer
Shin-ichi Kohno1, Chenhong Luo, Fumi Goshima
1Department of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Objectives:
To investigate the antitumor effects of the oncolytic herpes simplex virus (HSV) type 1 mutant HF10 on human and murine bladder cancer cells (T24 and MBT-2) in vitro and in immunocompetent mouse models.
Methods:
In vitro viral oncolytic activity and the replication ability of HF10 were measured in T24 and MBT-2 cells. To evaluate the therapeutic efficacy of HF10, disseminated peritoneal and bladder cancer models using MBT-2 cells were established in C3H/HeJ mice. The therapeutic efficacy was estimated from the survival rates and histopathologic analyses.
Results:
HF10 replicated well in both T24 and MBT-2 cells, and it induced extensive cell lysis. Treatment with HF10 significantly prolonged the survival periods and increased the survival rates in both models tested. Immunohistochemical studies showed that HSV antigens were detected in the bladders 1 and 3 days after intravesical treatment with HF10 in nonimmunized mice, but only at 1 day after HF10 treatment in preimmunized, HSV-1 antibody-positive mice. A large number of inflammatory cells infiltrated into the bladder mucosa at 3 days after HF10 treatment in the preimmunized mice.
Conclusions:
These results suggest that HF10, a novel oncolytic HSV-1 mutant, is a promising agent for the treatment of superficial bladder cancer.
Insights
The oncolytic herpes simplex virus (HSV) type 1 mutant HF10 demonstrated significant antitumor effects, prolonging survival in bladder cancer models. HF10 shows promise as a novel therapeutic agent for superficial bladder cancer.
Area of Science:
- Oncology
- Virology
- Immunology
Background:
- Bladder cancer remains a significant health concern with limited therapeutic options.
- Oncolytic viruses are emerging as a promising strategy for cancer treatment.
- Herpes simplex virus (HSV) type 1 mutants are being explored for their oncolytic potential.
Purpose of the Study:
- To evaluate the antitumor efficacy of the oncolytic HSV-1 mutant HF10.
- To assess HF10's effects on human (T24) and murine (MBT-2) bladder cancer cells in vitro.
- To investigate HF10's therapeutic potential in immunocompetent mouse models of bladder cancer.
Main Methods:
- In vitro assessment of HF10's oncolytic activity and replication in bladder cancer cell lines.
- Establishment of disseminated peritoneal and bladder cancer models in C3H/HeJ mice.
- Evaluation of therapeutic efficacy through survival rate analysis and histopathology.
Main Results:
- HF10 exhibited robust replication and induced significant cell lysis in both T24 and MBT-2 cells.
- Intravesical HF10 treatment significantly improved survival rates in mouse models.
- HSV antigen detection and inflammatory cell infiltration were observed in bladders post-treatment, varying with immunization status.
Conclusions:
- The oncolytic HSV-1 mutant HF10 demonstrates potent antitumor activity against bladder cancer.
- HF10 is a promising candidate for the treatment of superficial bladder cancer.
- Further research into HF10's immunomodulatory effects may enhance its therapeutic application.
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