Recombinant virus genome modification technology has gradually matured, greatly improving the effect, specificity and safety of oncolytic viruses in tumor treatment. Coupled with the mutual benefit of oncolytic viruses and traditional anti-tumor therapies, the prospects of oncolytic viruses are promising. Let us understand the development status of oncolytic viruses together and walk into Medicilon’s oncolytic virus research and development platform together.
Medicilon has always stood at the forefront of innovative drugs and built a platform for the efficacy of oncolytic viruses to help more innovative drug research and watch new drug development.
I Foreign clinical research progress
Herpes simplex virus type I-T-Vec
T-Vec is modified from the JS1 strain of herpes simplex virus type I (HSV-1). In 2015, the FDA approved the listing of T-Vecchio. In 2017, the European EMEA approved T-VEC for the treatment of unresectable stage IIIb, IIIc, and IVM1a melanomas that have not metastasized to bones, brain, lungs or other organs.
Herpes simplex virus type I-HF10 (C-REV)
C-REV is a spontaneous mutant of oncolytic herpes simplex virus type I (HSV-1). The Phase I clinical trial (NCT01017185) conducted in 2009 showed that the incidence of drug-related adverse events (AEs) was 34.6%, the response was mild, and the tolerance was good. CR (complete remission) and PR (partial remission) were not observed at the end of the clinical trial.
Pox virus Pexa-Vec (JX-594)
JX-594 is a vaccinia virus that has been genetically engineered. Up to now, JX594 has carried out a number of single and combined treatments for solid tumors such as liver cancer, kidney cancer and colorectal cancer.
Poliomyelitis virus PV1 (RIPO)
Poliomyelitis virus (poliovirus) is a natural pathogen that can selectively infect nerve cells. Gromeier et al. replaced the normal poliovirus IRES with rhinovirus IRES. The resulting PV1 (RIPO) virus can selectively destroy malignant glioma cells while ensuring that normal neuronal cells are not affected.
II Domestic clinical research progress
Binhui Biological Company’s OH2 injection
OH2 virus is genetic modification and transformation of type II herpes simplex virus strain HG52, so that the virus can selectively replicate in tumor cells and exert oncolytic effect. It can be inserted into the viral vector to express human granulocyte macrophage colony stimulating factor (hGM-CSF) gene, which promotes the body’s immune response induced by the destruction of tumor tissue and the release of tumor-associated antigens caused by virus replication.
OrienX010 from Aoyuan Heli
The main component of OrienX010 is HSV-1, its pathogenic genes have been deleted, and a DNA fragment encoding human granulocyte-macrophage colony stimulating factor (GM-CSF) has been inserted. OrienX010 for patients with liver metastases from melanoma is an open phase Ic trial. OrienX010 is injected into liver tumors. The overall effective rate is 12.5%, and the disease control rate (DCR) reaches 43.8%.
OHSV series (herpes virus)
Innomicro has developed a series of oHSV viruses. Innomicro scientists have constructed the first retargeted oHSV. In July 2019, T3011 passed the National Medical Products Administration (NMPA) New Drug Clinical Research Application (IND).
Tasly’s T601 (vaccinia virus)
In 2016, Tasly purchased the intellectual property rights of French Transgene poxvirus oncolytic virus vector. In July 2018, Tasly announced that it had obtained all the research, development and commercial rights of the oncolytic virus T601 (TG6002, oncolytic virus) and T101 (vaccine) in Greater China.
Combination therapy
Oncolytic virus and chemotherapy combination
Oncolytic adenovirus can significantly improve the killing effect of traditional chemotherapy on tumor cells, and chemotherapy drugs will not interfere with the replication and lysis of oncolytic adenovirus in tumor cells and the expression of therapeutic genes. Therefore, the specially constructed oncolytic adenovirus combined with chemotherapy to treat tumors works through different mechanisms and has a synergistic and enhanced effect on killing tumor cells. The efficacy is better than chemotherapy alone or viral gene therapy alone. However, oncolytic adenovirus combined with chemotherapy to treat tumors will also make the relationship between chemotherapy and oncolytic adenovirus treatment more complicated due to the cytotoxicity and pharmacokinetic characteristics of the virus itself.
Oncolytic virus and radiotherapy combination
Whether it is through radiation to enhance the oncolytic effect of the virus, or through the virus to enhance the sensitivity of cell radiotherapy, this combination scheme has shown synergistic anti-tumor effects in various studies. In order to enhance the combined effect of oncolytic virus therapy and radiotherapy, the virus can be modified, including modification of the promoter that can be activated after irradiation, or modification of genes that can activate cell death induced by radiation, the purpose is to increase the specificity of radiation to tumors Sex and lethality.
Combination of oncolytic virus and immunosuppressive therapy
Immunotherapy is hailed as a game-changing role in cancer treatment, but many patients have low or no response rates to treatments with checkpoint inhibitors such as the PD-1 antibody Keytruda. Oncolytic virus infection can release tumor antigens and attract immune cells to the tumor microenvironment, making it a “hot tumor” that responds to antibody therapy. In clinical practice, the concept of oncolytic virus combined with tumor immune checkpoint antibody has waited for effective verification therapy.
Oncolytic virus and CAR-T therapy combination
The long-lasting response of CAR-T cell therapy depends on the transport of donor T cells and survival in the tumor. Oncolytic viruses can reshape the local tumor microenvironment and improve T cell recruitment and effector functions; for oncolytic viruses, The combination of CAR-T cell therapy strategies can work in a complementary and additive manner, overcoming the limitations of oncolytic viruses’ limited anti-tumor effects on remote (untreated) sites.
Medicilon has a BSL2 laboratory and an ABSL2 negative pressure animal room in Chuansha Park, which are deployed and designed in accordance with biosafety level II standards, coupled with standardized process management and operations, providing a safe and stable research environment for oncolytic virus research .
Medicilon has a comprehensive and complete pharmacodynamic evaluation system for anti-tumor drugs, and has established more than 200 tumor evaluation models, including xenogeneic tumor transplantation models, orthotopic tumor transplantation models, allogeneic tumor transplantation models, transgenic mouse tumor models, Humanized tumor transplantation models, etc., provide a broad platform for the pharmacological research of oncolytic viruses.
Medicilon’s one-stop pre-clinical service platform can customize exclusive plans according to the characteristics of customers, arrange and implement the most reasonable trial plans, save customers worry and effort, and complete various pre-clinical research trials with high quality. Complete the declaration process in a short time.
Medicilon (stock code: 688202) is a drug development outsourcing service company (CRO). Founded on February 2, 2004, the company has gone through 16 years and established a company in Shanghai that integrates compound synthesis, compound activity screening, structural biology, pharmacodynamic evaluation, pharmacokinetic evaluation, toxicology evaluation, and formulation research A comprehensive technical service platform that conforms to international standards and is integrated with new drug registration, and has been recognized by the international drug management department. Medicipua’s animal laboratory facilities have obtained AAALAC (International Association for Animal Evaluation and Certification) certification and National Medical Products Administration NMPA GLP certification, and have reached the US Food and Drug Administration GLP standard.
Medicilon has a wealth of experience in global cooperation. Since 2015, Medicilon has served more than 500 active customers worldwide. It has served many global pharmaceutical companies such as Takeda Pharmaceuticals, Johnson & Johnson Pharmaceuticals, GlaxoSmithKline, Roche Pharmaceuticals, etc. R&D outsourcing services are provided by well-known domestic and foreign customers such as Swiss Medicine, Yangzijiang Pharmaceutical, CSPC, Huahai Pharmaceutical, and Zhongsheng Pharmaceutical.
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