Another lysovirus product was approved in China clinically carrying four immune factors.

On September 17th, VG161, a meso-born resuscant, was approved clinically in China to develop a treatment for advanced malignant solid tumors with injectable lesions.
VG161 carries genes from both IL12, IL15/15RA (IL15 and IL15 subjects alpha subbil) and PD-L1 blocking peptides (PDL1B), the world's first product to carry four immunokines, according to a press release.
the news has once again drawn attention to lysovirus therapy.
, as the name suggests, refers to a class of viruses that can effectively infect and destroy cancer cells.
, lysoviral therapy has become an important research field in the field of tumor immunotherapy.
In recent years, a number of large pharmaceutical companies, including BMS, Johnson and Johnson, MSD and AbbVie, have added codes through acquisitions or partnerships.
in China, in addition to meso-rehabilitation, 3D biology, also noo medicine, Ano medicine, etc. are also involved in the development of such drugs.
, what is unique about lysoviral therapy? Why is it popular with many biopharmaceutical companies? The concept of immunotherapy "to kill cancer" has been around for a long time.
as early as the 1950s, scientists observed that tumors in the body receded during infection, leading to the idea of using the virus to treat cancer.
in lysovirus therapy, lysovirus plays a central role.
is a specially designed virus that tends to infect tumor cells and is weak in normal cytotoxicity, selectively replicating and multiplying in large numbers within tumor cells until cancer cells cleavage and die.
when cancer cells rupture and die under infection, newly generated virus particles are released, further infecting surrounding cancer cells.
More interestingly, the study found that lysovirus can be given special functions while infecting and killing cancer cells, such as autologous vaccines for tumor lysis antigens in the host in place, immunomodulation factors, etc., which in turn promote the activation of anti-tumor-specific immune responses in patients.
these characteristics, lysoviral therapy has been classified as an important branch of tumor immunotherapy.
The basic principles of lysozyrovirus immunotherapy (Photo: Replimune Company's official website) In summary, lysozyrovirus immunotherapy has a dual anti-cancer mechanism: they can not only cause cancer cell cleavage death through the infection of lysovirus infection into the tumor, but also express tumor-specific immunoactivated proteins and stimulate a systemic anti-tumor immune response.
three have been approved for listing worldwide, and one from China shows that at least three lysovirus therapies have been approved for listing worldwide: Rigvir, Acorine (E1B-55KD, Oncorine), and Imlygic (talimogene laherparepvec, T-Vec).
1, Rigvir Rigvir, a genetically modified ECHO-7 enterovirus developed by Latvian company Latima, was approved in Latvia in 2004 for the treatment of melanoma.
the drug has been approved in several countries, including Poland and Armenia.
Clinical cases over the past decade have shown that Rigvir lysomavirus is safe and effective, can improve the survival rate of melanoma patients by 4-6 times, and has obvious effect on gastrointestinal tumors, pancreatic cancer, bile tube cancer and malignant sarcoma and other solid tumors.
it is worth mentioning that during the 2nd Expo in November 2019, Guizhou Shengno Pharmaceuticals signed a cooperative development agreement with Latima, which acquired Rigvir's exclusive interest in Greater China.
agreement, the two sides will jointly promote Rigvir's registration declaration and exploratory applications in China, and further study the new lysovirus and new adaptations to jointly develop the global market.
2, Ankeri Ankeri is a recombinant human type 5 adenovirus injection of Shanghai 3D Biological Company.
public information shows that Acre is the use of genetic engineering technology to remove the human type 5 adenovirus E1B-55kD gene fragments and E3-19KD gene fragments re-obtained a tumor adenovirus, in the p53 gene deficiency or abnormal tumor can be specifically copied and produce replication-dependent cytotoxic effect, but no obvious cytotoxic effect on normal human cells.
the drug was first approved in China in 2005 and can be used to treat head and neck tumors, liver cancer, pancreatic cancer, cervical cancer and other adaptive disorders.
3, Imlygic Imlygic is a genetically modified type 1 herpes simplex virus (HSV-1) developed by Amgen that replicates and expresses immune-activated protein granulocyte-macrophage cluster stimulation factor (GM-CSF) in tumor cells.
direct injection into melanoma lesions can cause the tumor cells to dissolve, causing the tumor cells to rupture and release tumor-origin antigens and GM-CSF, speeding up the immune response to the tumor.
Imlygic was approved in the U.S. in October 2015 for a late-stage melanoma that relapses after topical therapy, the first FDA-approved treatment for the virus.
BMS, Johnson and Johnson, Mercedon and other large pharmaceutical companies have joined since the FDA approved the first lysovirus therapy in 2015, this innovative therapy has received the attention of many large pharmaceutical companies.
recent years, a number of large pharmaceutical companies, including BMS, Johnson and Johnson, and Mercado, have entered the field through acquisitions or partnerships, according to public information released by the Company.
1, BMS signed a partnership agreement with PsiOxus Therapeutics, a company dedicated to developing innovative cancer immunotherapy, to obtain NG-348, the latter's anti-cancer lysovirus candidate, with an advance payment of $50 million and a milestone payment of $886 million.
NG-348 was developed based on PsiOxus' first-generation lysovirus product, enadenotucirev, and its unique cancer immunotherapy technology platform.
NG-348, based on enadenotucirev, inserts two gene fragments, Anti-CD3 and CD80, that encode T-cell activation media, to drive T-cells' immune response in the tumor microenvironment and enhance their ability to kill cancer cells.
2, 2017, AbbVie announced a global research and development partnership with Turnstone Biologics, Inc., which specializes in next-generation lysosovirus therapies, for exclusive development rights to three of its next-generation lysovirus immunotherapies.
lysovirus therapy developed by Turnstone is based on genetically engineered Maraba Virus.
the company's lysovirus therapy differs from other therapies in that it integrates tumor vaccines with cancer virus therapies.
in the modified Malaba virus, the researchers also added a sequence of expression tumor antigens.
this transformation allows these Malaba viruses to express tumor antigens on the surface of the virus and present them to the patient's immune system, thereby stimulating an immune response to the tumor.
immune system can not only further kill tumors, but also the memory effect of immune cells can prevent cancer recurrence.
, In February 2018, Mercadon acquired Viraltics, a company focused on developing immunotherapy for cancer-soluble tumors, for $394 million through its subsidiary.
Its main candidate, CAVATAK, is a proprietary agent for common cold Kosage virus A21 (CVA21), which binds to specific subject proteins that are highly expressed on multiple types of cancer cells and kills local and metastasis cancer cells through cell lysation and potentially immune responses to cancer cells.
, CAVATAK is currently being evaluated in a number of clinical trials as an intracerine and intravenous preparation, including in combination with Mercadon's heavy-weight anti-PD-1 therapy, Keytruda (pembrolizumab).
2018, Janssen, a company owned by Johnson and Johnson, bought BeneVir Biopharm, a lysovirus immunotherapy company, for $1 billion.
BeneVir, Inc., which specializes in the development of lysovirus therapies, uses its proprietary T-Stealth lysovirus platform to design lysate viruses that infect and destroy cancer cells.
, the T-Stealth lysovirus can evade the immune system, destroying cancer cells directly or by activating the immune system.
As a result, this technology platform reduces antagonistic effects between lysovirus and immuno-checkpoint inhibitors, making simultaneous use of lysovirus and immuno-checkpoint inhibitors possible and maximizing synergetic clinical mitigation.
2018, Boehringer Ingelheim bought Vira Therapeutics for 210 million euros.
ViraTherapeutics is a biopharmaceutical company dedicated to the development of lysovirus therapies, and its main candidate, VSV-GP, is the vesicle-based oral inflammatory disease virus (VSV) containing modified glycoprotein (GP), which is currently being evaluated in clinical trials as a single therapy or combination therapy.
6, Takeda and Turnstone, a company focused on the development of lysoviral therapy, reached a global partnership license agreement to jointly develop and promote the latter's new viral immunotherapy RIVAL-01.
RIVAL-01 is turnstone's leading drug candidate based on its bovine pox virus platform.
it encodes three powerful immunomodulants, IL-12 cytokines, FLT3 supplements and CTLA-4 antibodies, which together drive immune activity and reshape the tumor microencology to eradicate the tumor.
when the bovine pox virus replicates in cancer cells throughout the body, the genetically modified organisms it carries will also be expressed.
the production of its coded regulator at the tumor site increases the virus's inherent solute and microenvironment modification properties, thus forming a multi-mechanism attack on the tumor.
addition, there are many new developments focused on this innovative therapy, including Calidi Biotherapeutics, Oncorus, Replimune Group, and more.
Chinese companies to join the research and development army In recent years, many Chinese companies have also joined the research and development of lysovirus therapy.
public information shows that a number of companies, such as Biopharmaceuticals, Tiansli, Ano Pharmaceuticals, have introduced different types of lysovirus products (see table below).
Reolysin, introduced by Ano Pharmaceuticals, is a second-generation lysovirus tumor immunotherapy developed based on the mammalian intestinal virus that kills cancer cells that are overactivated by the RAS signaling path.
the drug has been granted fast-track status by the FDA to treat metastasis breast cancer.
In addition, there are many Chinese pharmaceutical companies in the choice of independent research and development of lysolytic virus therapy, including 3D biology, Tiandakang gene, Dabo biology, Kanghong biology, ino-micro medicine, bino bio, meso-rehabilitation biology, Lepu biology and so on.
3D organisms have developed H102 (tumor-targeted recombinant adenovirus injections) and H103 (tumor-based recombinant adenovirus injections) on this basis, in addition to the aforementioned approved lysovirus therapy, Acrey.
VG161, which has just been approved for clinical practice in China, is a new type of anti-tumor immuno-enhanced type I herpes simplex lysoma virus that carries the genes of IL12, IL15/15RA (IL15 and IL15 subject alpha sub-base) and PD-L1 blocking peptide (PDL1B).
the drug had previously been approved clinically in Australia, the first in the world to carry four immunokines, according to a press release.
future of lysolytic immunotherapy Although single dose use of lysolytic immunotherapy has shown clinical activity, the researchers found that the combination of lysovirus therapy and immuno-checkpoint inhibitors could further enhance the effectiveness of treatment.
this potential has also been proven in clinical trials.
studies have found that both PD-1 inhibitors and CTLA4 inhibitors, in the case of ilygic, can increase the number of CD8 and CD4-positive T cells in patients, indicating that there may be a systemic immune effect.
addition, patients with low immunocellular immersion also achieved good results, indicating that "cold tumors" also responded to immuno-checkpoint inhibitors under the influence of lysovirus.
According to a review published in June 2018 by Nature Reviews Cancer, lysovirus therapy has two potential development directions: first, in combination with T-cell therapy to assist T-cells in the proliferation, movement, and efficacy of local tumor microenvironments;
: Luke Russell 1 and Kah-Whye Pen. (2018). The emerging role of oncolytic virus therapy against cancer. Chin Clin Oncol . doi:10.21037/cco.2018.04.04. [2] Fukuhara, H., Ino, Y., and Todo, T. (2.