Effective treatment of disseminated peritoneal colon cancer with new replication-competent herpes simplex viruses

Hideto Kimata1, Hiroki Takakuwa, Fumi Goshima

  • 1Laboratory of Virology, Research Institute for Disease, Mechanism and Control, Department of Surgery II, Graduate School of Medicine, Nagoya University, Showa-ku, Nagoya 466-8550, Japan.

Abstract

Insights

New herpes simplex virus (HSV) mutants, HF10 and Hh101, show promise for oncolytic viral therapy. These safe and effective HSV mutants demonstrate efficacy in treating malignant tumors and inducing anti-tumor immunity.

Area of Science:

  • Virology
  • Immunology
  • Oncology

Background:

  • Oncolytic herpes simplex virus type 1 (HSV-1) mutants are investigated for cancer therapy.
  • Therapeutic efficacy relies on viral replication within tumors and stimulating host anti-tumor immune responses.

Purpose of the Study:

  • To evaluate the oncolytic activities of novel replication-competent, attenuated HSV mutants, HF10 and Hh101.
  • To assess their safety and effectiveness in treating malignant tumors.

Main Methods:

  • Genome structures of HF10 and Hh101 mutants were determined.
  • Mice with disseminated peritoneal carcinoma and sarcoma were treated with the mutants.
  • Tumor histology and immunohistochemistry were used for examination.

Main Results:

  • HF10 and Hh101 effectively treated disseminated peritoneal colon carcinoma in a BALB/c mouse model.
  • Surviving mice in the BALB/c model developed resistance to tumor cell rechallenge.
  • HF10 improved survival rates in a C3H mouse model, while Hh101 did not.

Conclusions:

  • HF10 and Hh101 represent novel, safe, and effective HSV mutants for oncolytic viral therapy.
  • Hh101 exhibits greater attenuation than HF10 due to its double gene knockout.
  • The selection of an appropriate viral mutant should be tailored to the specific type of malignancy.