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 both Japan and the U.S., Takara Bio has been conducting C-REV clinical development program. In Japan, we are currently conducting a Phase II clinical trial targeting malignant melanoma and a Phase I clinical trial targeting pancreatic cancer. In the U.S., we conducted a Phase II clinical trial of C-REV in combination with Ipilimumab 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, 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
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
Illinois, 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
Oncolytic Virotherapy Summit
December 5 - 7, 2017
Miami, U.S.A.
Development Strategy of HF10, a spontaneous mutant Herpes Simplex Virus
ESMO (European Society for Medical Oncology) Asia 2017 Congress
November 17 - 19, 2017
Suntec, Singapore
Final Results of a Phase II Multicenter Trial of HF10, Oncolytic Virus immunotherapy, and Ipilimumab Combination Treatment in Patients with Stage IIIB-IV Unresectable or Metastatic Melanoma
Final Results of Phase I Trial of HF10, Oncolytic Virus Immunotherapy, in Japanese Patients with Refractory Superficial Cancers
The 55th Annual Meeting of Japan Society of Clinical Oncology
October 20 – 22, 2017
Yokohama, Japan
Final Results of a Phase II Multicenter Trial of HF10, a Replication-competent HSV-1 Oncolytic Virus, and Ipilimumab Combination Treatment in Patients with Stage IIIB-IV Unresectable or Metastatic Melanoma
Phase I Trial of HF10, a Replication-competent HSV-1 oncolytic Immunotherapy, in Patients with Refractory Superficial Cancers
The Society of Melanoma Research
October 18 – 21, 2017
Brisbane, Australia
A Phase II Multicenter Trial of HF10, Oncolytic Virus Immunotherapy, and Ipilimumab Combination Treatment in Patients with Stage IIIB-IV Unresectable or Metastatic Melanoma
The 23rd International Pigment Cell Conference
August 26 - 30, 2017
Denver, U.S.A.
(Click here for abstract)
Final Results of a Phase II Multicenter Trial of HF10, Oncolytic Virus Immunotherapy, and Ipilimumab Combination Treatment in Patients with Stage IIIB-IV Melanoma
The 15th Annual Meeting of Japanese Society of Medical Oncology (JSMO)
July 27 - 29, 2017
Kobe, Japan
(Click here for presented data)
Phase I Trial of Oncolytic Immunotherapy HF10 in Patients with Refractory Superficial Cancers
The 23rd Annual Meeting of
Japan Society of Gene and Cell Therapy
July 20 – 22, 2017
Okayama, Japan
Symposium 9-4
Clinical trial data using HF10, the oncolytic herpes simplex virus
The 33rd Annual Meeting of the Japanese Skin Cancer Society
June 30 - July 1 , 2017
Akita, Japan
Oncolytic virus therapy of HSV-1
~ for the treatment of malignant melanoma
2017 ASCO (Annual Meeting - American Society of Clinical Oncology)
June 2 -
.6, 2017 Chicago, U.S.A.
(Click here for presented data)
Final Results of a Phase II Multicenter Trial of HF10, a Replication-competent HSV-1 Oncolytic Virus, and Ipilimumab Combination Treatment in Patients with Stage IIIB-IV Unresectable or Metastatic Melanoma

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