What's so magical about the new treatment of "detoxifying cancer" that multinational drug companies are laying out?

From now: Medical mission
July 2019, scientists at a research institute found that a common cold virus can target cancer cells in patients infected with and destroyed bladder cancer, and that the signs of cancer in a bladder cancer patient who participated in the trial have disappeared altogether. This "detoxifying cancer" treatment is the solution to the tumor virus therapy.
tumor virus, as the name suggests, refers to a class of viruses that can effectively infect and destroy cancer cells. Tumor virus immunotherapy has a dual anti-cancer mechanism: they can not only cause cancer cell lysis death through the proliferation of tumor virus in tumors, but also release tumor-specific immunoactivated proteins, stimulate systemic anti-tumor immune response.
at present, tumor virus therapy has become an important research field in the field of tumor immunotherapy. A number of large pharmaceutical companies, including BMS, Johnson and Johnson, and MSD, have all added code in recent years through acquisitions or partnerships. In China, many biopharmaceutical companies, including 3D Biology, Tianshili, Yino Micro Pharma and Arnault Pharmaceuticals, have also been involved in the development of these drugs through independent research or overseas introduction.The concept of
lysoma virus therapy has been around for a long time. As early as the 1950s, scientists observed that cancer patients' tumors fade during the virus, leading to the idea of treating cancer with the virus.
the tumor virus plays a central role in tumor-soluble virus therapy. Tumor virus is a specially designed virus, it is more inclined to infect tumor cells and normal cytotoxicity is very weak, can selectively replicate and reproduce in tumor cells in large numbers, until cancer cells lysate, death. When cancer cells break and die under the virus, newly generated virus particles are released, further infecting the surrounding cancer cells. More interestingly,
study found that the tumor virus can be given special functions when infected and kills cancer cells, such as autovaccines and immunomodulators that can be expressed in host situ against tumor lysis antigens, which in turn promote the activation of the anti-tumor-specific immune response in the patient. Based on these characteristics, tumor-soluble viral therapy has been classified as an important branch of tumor immunotherapy.. In order to make the tumor virus effectively target cancer cells, the specific targeting of tumors is a major focus in research and development. Interestingly, tumors are inherently vulnerable to tumor viruses - when genes such as RAS, TP53, RB1, and PTEN mutate, the cancer cells' ability to fight hiv infection weakens, giving the tumor virus a chance.
these weaknesses against cancer cells, researchers have developed a variety of viruses that can effectively target tumors. For example, modified bombviruses such as the herpes stomatitis virus and the Malaba virus can specifically target cancer cells by relying on defects in interferon signaling pathways. The first FDA-approved melanoma virus was modified by herpes simplex virus (HSV-1). These viruses are designed to be related to the immune response.
, there are some tumor viruses that can be additionally targeted at metabolic abnormalities of malignant tumors. Pexa-Vec, for example, has a defective thoratosin kinase gene of its own, so it can only be replicated in cancer cells with excess thoratosin kinase activity. In addition, the B18R gene in this virus has an early termination cryptoon, making its encoded protein less susceptible to interferon identification and binding. These properties allow such viruses to be effective at targeting tumor cells with minimal impact on normal cells.
so far, three solution therapies have been approved for sale worldwide: Rigvir, E1B-55KD, Oncorine, and Imligic (talimogene laherparearepvec, T-Vec).
Rigvir is a genetically modified ECHO-7 enterovirus developed by The Latvian company Latima and was approved in Latvia in 2004 for the treatment of melanoma. The drug has been approved in several countries, including Poland and Armenia. The clinical cases of the past ten years have proved that Rigvir tumor virus is safe and effective, can improve the survival rate of melanoma patients 4-6 times, and has obvious effect on gastrointestinal tumor, pancreatic cancer, bile duct cancer and malignant sarcoma and other solid tumors.
it is worth mentioning that during the second Expo in November 2019, Guizhou Shengno Pharma and Latima Signed a cooperative development agreement, which acquired Rigvir's exclusive rights in Greater China. Under the agreement, the two sides will jointly promote Rigvir's registration and exploratory application in China, and further study new mechanisms and new indications of the fibroid virus to jointly develop the global market.
Ankeri is a recombinant human type 5 adenovirus injection from Shanghai 3D Bio. Public information shows that Ankeri is using genetic engineering technology to remove human type 5 adenovirus E1B-55kD gene fragments and E3-19KD gene fragments after the reacquired asoma adenovirus, which in the p53 gene deficiency or abnormal tumor can specifically replicate and produce replication-dependent cell toxiceffect, and no obvious cell toxic 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 indications.
Imlygic is a genetically modified herpes simplex 1 virus (HSV-1) developed by Amgen that replicates and expresses immunoactivated protein granulocytes-macrophages cluster irritants (GM-CSF) within tumor cells. Injecting it directly into the melanoma lesions can cause tumor cells to dissolve, causing tumor cells to rupture, and releasing tumor-derived antigens and GM-CSF, accelerating the immune response to the tumor. Imlygic was approved in the United States in October 2015 for late-stage melanoma, which recurred after local treatment, the first FDA-approved solution to the virus.
Since the FDA approved the first tumor-soluble virus therapy in 2015, the innovative treatment has received the attention of many large pharmaceutical companies. Public information shows that in recent years, 100-times Meimei Shiguibao (BMS), Johnson and Johnson, Mersadong and many other large pharmaceutical enterprises, have been through the acquisition or cooperation of the way, plus code in this area.
December 2016, Baxter and PsiOxus Therapeutics entered into a cooperation agreement. BMS obtained PSiOxus Therapeutics' cancer lysoma virus candidate NG-348 and paid the latter a $50 million advance payment to fund preclinical research on the drug. In addition, BMS will pay $886 million in milestones to support the subsequent development and commercialization of NG-348.
PsiOxus, which is working on innovative cancer immunotherapy, was shortlisted for the 2017 Fierce Biotech 2017 Fierce 15. NG-348 is based on the company's first generation of tumor-soluble virus productenadenoticrev and its unique oncology immunotherapy technology platform. NG-348 inserts two gene fragments that encode T-cells to activate ligands, which activate CD3 and CD28 receptors on the surface of T cells, respectively, and boost the immune response of T cells in the tumor microenvironment, enhancing their ability to kill cancer cells.
October 2017, AbbVie announced a global research and development cooperation agreement with Turnstone Biologics, which has acquired the exclusive development rights to the latter's three-generation protozoa immunotherapy. Founded in 2015, Turnstone is a clinical development company focused on the next generation of tumor-soluble viral therapy, which was also shortlisted for the 2017 Biotech Mammoth Company.
Turnstone developed the solution is based on genetically engineered Maraba Virus. The difference between the company's tumor-soluble virus therapy and other therapies is that it integrates tumor vaccines with cancer viral therapies. In the modified Malaba virus, the researchers also added a sequence that expressed tumor antigens. This modification allows these malaba viruses to express tumor antigens on the surface of the virus and present them to the patient's immune system, stimulating an immune response to the tumor. The activated immune system not only has the effect of further killing tumors, but also the memory effect of immune cells prevents cancer recurrence.
February 2018, Mersadon acquired Viraltics for $394 million through its subsidiary. Viralytics is a company focused on developing cancer solubility immunotherapy. Its main candidate, CAVATAK, is a proprietary formulation of the common cold Cosage virus A21 (CVA21), which binds to specific receptor proteins highly expressed on multiple types of cancer cells and kills local and metastatic cancer cells through cell lysis and an immune response that is potentially targeted at cancer cells.
currently, CAVATAK is currently being evaluated in a number of clinical trials as an intratumor and intravenous agent, including in conjunction with Mercado's heavy anti-PD-1 therapy Keytruda (pembrolizumab).
May 2018, Janssen, a Johnson and Johnson company, bought BeneVir Biopharm, a virus immunotherapy company, for $1 billion. BeneVir focuses on the development of tumor-soluble virus therapy, and its proprietary T-Stealth tumor virus platform is designed to infect and destroy cancer cells. According to reports, t-Stealth tumor virus can evade the immune system, so directly or by activating the immune system to destroy cancer cells. As a result, this technology platform reduces the antagonism between the fibroid virus and immunocheckpoint inhibitors, making it possible to use the tumor virus and immunocheckpoint inhibitors simultaneously, and maximizes synergy clinical mitigation.
September 2018, Boehringer Ingelheim bought Vira Therapeutics for 210 million euros. ViraTherapeutics, a biopharmaceutical company dedicated to the development of tumor virus therapy, is whose main candidate, VSV-GP, is the vesicle-based ventritis virus (VSV) containing improved glycoprotein (GP), which is currently being evaluated in clinical trials as a separate or combination therapy.
December 2019, Takeda and Turnstone, a company focused on the development of solute virus therapy, entered into a global cooperative license agreement to jointly develop and promote the latter's new viral immunotherapy RIVAL-01. Under the agreement, Takeda will pay An advance of $120 million to Turnstone and acquire a stake in its new partner for a global exclusive license from RIVAL-01.
RIVAL-01 is a leading candidate for Turnstone based on its bovine pox virus platform. It encodes three powerful immunomodulators, IL-12 cytokines, FLT3 ligands and CTLA-4 antibodies, and together drives immune activity and reshapes the tumor microenvironment to eradicate tumors. When the bovine pox virus replicates in cancer cells throughout the body, the genetically modified organisms it carries are also expressed. The production of the encoded regulator at the tumor site increases the inherent tumor and microenvironment modification properties of the virus, thus forming a multi-mechanism attack on the tumor.
, there are many new talents focused on the development of this innovative therapy, including Calidi Biotherapeutics, Oncorus, Replimune Group, and more. These companies are also favoured by capital, such as Calidi, which completed round A financing in January and $79.5m on Oncorus in August last year.
in recent years, many Chinese companies have also joined the development of tumor virus therapy. Public information shows that Tianshili, Shengno Pharmaceuticals, Arnold Pharmaceuticals and other companies have introduced different types of tumor virus products through the "License-in" approach (see table below). Among them, Tianshili just introduced in May from Takara Bio, Japan, the tumor virus product C-REV, is a type 1 herpes simplex virus (HSV-1) detoxifying strain, can selectively replicate and break down tumor cells in tumor cells without damaging normal cells, C-REV is being developed to treat pancreatic cancer and melanoma. Reolysin, introduced by
Arnold Pharmaceuticals, is a second-generation tumor immunotherapy for the solute virus, which is based on the mammalian exorcisaring virus and kills cancer cells that are overactivated by the RAS signaling pathway. The drug has been granted fast-track status by the FDA for the treatment of metastatic breast cancer.
in addition, there are many Chinese pharmaceutical enterprises in the choice of independent research and development of tumor-soluble virus therapy, including 3D biology, Tiandakang gene, Dabo bio, Kanghong biological, Yino micro-medicine, Binhebio, renogym bio, Lepu biology and so on. In addition to the aforementioned approved tumor virus therapy Ankeri, 3D organisms have also developed H102 (tumor-targeted recombinant adenovirus injection) and H103 (tumor recombinant adenovirus injections) on this basis, which is still in the early stage of research. Tiandakang Gene, Kanghong Biology, Binhebio, etc. have been approved for clinical studies on the development of dissolved tumor virus products.
Although monodose use of tumor immunotherapy has shown clinical activity, the researchers found that combining tumor virus therapy with immunodot inhibitors could further enhance the effectiveness of the treatment. This potential has also been validated in clinical trials. The study found that both PD-1 inhibitors and CTLA-4 inhibitors, in combination with Imlygic, increased the number of CD8 and CD4-positive T cells in patients, indicating that systemic immune effects may be associated. In addition, patients with low immunocellular immersion also achieved good results, showing that under the action of the tumor virus, "cold tumor" also responded to immunocheckpoint inhibitors.
according to a review published by Nature Reviews Cancer in June 2018.