TAKARATAKARA BIO INC.

Canerpaturev(C-REV)

Outline

Canerpaturev(C-REV) is an attenuated strain of the herpes simplex virus type 1 (HSV-1) that demonstrates anti-tumor activity when locally injected into a tumor. This type of virus is called �oncolytic virus.� Oncolytic viruses do not replicate inside of normal cells while selectively replicate in tumor cells and break them down without excessively damaging normal cells. Many oncolytic viruses are engineered with gene recombination or foreign gene insertion, but C-REV is a spontaneously mutated virus that has never been genetically engineered. Therefore, C-REV is not subjected to regulations on the use of living modified organisms such as Cartagena Protocol on Biosafety to the Convention on Biological Diversity.

In Japan, Takara Bio is currently conducting a Phase I clinical trial targeting pancreatic cancer. In both Japan and the U.S., we conducted Phase II clinical trials of C-REV targeting malignant melanoma. The data showed a favorable benefit/risk profile and promising antitumor activity. This project in Japan has been developed in collaboration with Otsuka Pharmaceutical Co., Ltd.

Mode of action

When locally injected into a tumor, C-REV shows two different effects as described below.

  • Anti-tumor effect where oncolytic viruses selectively replicate in tumor cells and break them down without damaging to normal cells.
  • Systemic anti-tumor effects by activated cytotoxicT-lymphocytes following tumor destruction.

In clinical trials targeting solid tumors and melanoma in the U.S., there are some cases indicating tumor shrinkage even on uninjected tumors. This therapeutic approach using oncolytic virus has been rapidly drawing attention as a promising future immunotherapy.
C-REV is one of entirely new cancer immunotherapy which shows systemic anti-tumor immune response as well as local oncolytic tumor destruction.

Reference information
Articles
  • Eissa IR, Mukoyama N, Abdelmoneim M, Naoe Y, et al. Oncolytic herpes simplex virus HF10 (canerpaturev) promotes accumulation of CD8+ PD-1- tumor-infiltrating T cells in PD-L1- enriched tumor microenvironment, Int. J. Cancer. 2021.
  • Esaki S, Goshima F, Nishiyama Y, Kimura H, et al. Oncolytic activity of HF10 in head and neck squamous cell carcinomas. Cancer Gene Ther. 2019 Sep 3
  • Wu Z, Ichinose T, Naoe Y, et al. Combination of Cetuximab and OncolyticVirus Canerpaturev Synergistically Inhibits Human Colorectal Cancer Growth. Molecular Therapy. 2019, 13, 107-115
  • Eissa IR, Bustos-Villalobos I, Kodera Y, Kasuya H, et al. The Current Status and Future Prospects of Oncolytic Viruses in Clinical Trials against Melanoma, Glioma, Pancreatic, and Breast Cancers. Cancers 2018, 10, 356
  • Hirooka Y, Kasuya H, Kodera Y, Goto H, et al. A Phase I clinical trial of EUS-guided intratumoral injection of the oncolytic virus, HF10 for unresectable locally advanced pancreatic cancer. BMC Cancer 2018, 18, 596
  • Eissa IR, Kasuya H, et al. Genomic Signature of the Natural Oncolytic Herpes Simplex Virus HF10 and Its Therapeutic Role in Preclinical and Clinical Trials. Front Oncol. 2017, 7, 149
  • Hotta Y, Kasuya H, Kodera Y, et al. Curative effect of HF10 on liver and peritoneal metastasis mediated by host antitumor immunity. Oncolytic Virother. 2017, 6, 31-38.
  • Kasuya H, Goto H, Nishiyama Y, et al. Phase I dose-escalation clinical trial of HF10 oncolytic herpes virus in 17 Japanese patients with advanced cancer. Hepato-Gastroenterology. 2014, 61, 599-605
  • Tan G, Kasuya H, Kodera Y, et al. Combination therapy of oncolytic herpes simplex virus HF10 and bevacizumab against experimental model of human breast carcinoma xenograft. Int J Cancer. 2015, 136(7), 1718-1730.
  • Ishihara M, Seo N, Shiku H, et al. Systemic CD8+ T cell-mediated tumoricidal effects by intratumoral treatment of oncolytic herpes simplex virus with the agonistic monoclonal antibody for murine glucocorticoid-induced tumor necrosis factor receptor. PLoS One. 2014, Aug 8, 9(8), e104669.
  • Watanabe D, Goshima F, Nishiyama Y, et al. Oncolytic virotherapy for malignant melanoma with herpes simplex virus type 1 mutant HF10. J Dermatol Sci. 2008, 50(3), 185-196
  • Takakuwa H, Goshima F, Nishiyama Y, et al. Oncolytic viral therapy using a spontaneously generated herpes simplex virus type 1 variant for disseminated peritoneal tumor in immunocompetent mice. Arch Virol. 2003, 148, 813-825.
  • Jiang YM, Daikoku T, Nishiyama Y, et al. Growth and cytopathogenicity of herpes simplex virus in a macrophage cell line, RAW264: A good indicator of intraperitoneal pathogenicity. Microbiol Immunol. 1995, 39 (11), 905-909
Information of academic conferences
Conference Tittle
The Society for Melanoma Research
November 20 - 23, 2019
Salt Lake City, U.S.A.
Neoadjuvant Trial of Nivolumab in Combination with Canerpaturev (C-REV) Oncolytic Viral Therapy in Resectable Stage IIIB, IIIC, IVM1a Melanoma
ESMO (European Society for Medical Oncology) 2019 Congress
September 27 - October 1, 2019
Barcelona, Spain
Results from phase I study of the oncolytic immunotherapy agent Canerpaturev (C-REV) in combination with gemcitabine plus nab-paclitaxel as first-line treatment of unresectable pancreatic cancer
(Click here for presented data)
Phase I study of the oncolytic viral immunotherapy agent Canerpaturev (C-REV) with S-1 in patients with stage IV pancreatic cancer
(Click here for presented data)
Final Results from Phase II of Combination with Canerpaturev (formerly HF10), an Oncolytic Viral Immunotherapy, and Ipilimumab in Unresectable or Metastatic Melanoma in 2nd-or later line treatment
(Click here for presented data)
2019 ASCO (Annual Meeting - American Society of Clinical Oncology)
May 31 - June 4, 2019
Chicago, U.S.A.
(Click here for presented data)
Immunological impact of canerpaturev (C-REV, formerly HF10), an oncolytic viral immunotherapy, with or without Ipilimumab (Ipi) for advanced solid tumor patients (pts)
2019 ASCO-GI (American Society of Clinical Oncology Gastrointestinal Cancers Symposium)
January 17 - 19, 2019
San Francisco, U.S.A.
(Click here for presented data)
Results from Phase I study of the oncolytic viral immunotherapy agent Canerpaturev (C-REV) in combination with Gemcitabine plus Nab-paclitaxel for Unresectable Pancreatic Cancer
ESMO (European Society for Medical Oncology) 2018 Congress
October 19 - 23, 2018
Munich, Germany
(Click here for presented data)
Topline Results from Phase II of Combination Treatment with Canerpaturev (HF10), an Oncolytic Viral Immunotherapy, and Ipilimumab in Patients with Unresectable or Metastatic Melanoma after Anti-PD-1 Therapy
The 24th Annual Meeting of Japan Society of Gene and Cell Therapy
July 26 - 28, 2018
Tokyo, Japan
Clinical evaluation of a novel oncolytic viral immunotherapy agent, Canerpaturev (HF10)
The 34th Annual Meeting of the Japanese Skin Cancer Society
July 6 - 7 , 2018
Shizuoka, Japan
Novel cancer therapy for malignant melanoma "Oncolytic virus immunotherapy"
2018 ASCO (Annual Meeting - American Society of Clinical Oncology)
June 1 - 5, 2018
Chicago, U.S.A.
(Click here for presented data)
Efficacy and Genetic Analysis for a Phase II Multicenter Trial of HF10(Canerpaturev), a Replication-competent HSV-1 Oncolytic Immunotherapy, and Ipilimumab Combination Treatment in Patients with Stage IIIB-IV Unresectable or Metastatic Melanoma

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