based on adenovirus specific highly active oncolytic virus
According to the 2020 Global Cancer Report released by the International Agency for Research on Cancer (IARC) of the World Health Organization, the number of patients diagnosed with cancer worldwide in 2020 reached 19.29 million, and nearly 10 million people died of cancer, of which 3 million people died of cancer in China, accounting for 30% of the total number of cancer deaths in the world. China leads the world in new cancer cases and deaths. In 2021, the global anti-tumor drug industry market size reached 180.7 billion US dollars, an increase of 20.2%, the global anti-tumor drug market is mainly concentrated in the United States and China, the United States accounted for 46.7%, China is 19.6%. Compared with other tumor therapies, oncolytic virus drugs have the advantages of good targeting, high safety, less side effects and lower price than other innovative therapies. According to the 2020 China oncolytic virus drug industry research report, the domestic market size increased from 270 million yuan to 670 million yuan in 2015-2019, with a compound annual growth rate of 25.7%. With the expansion of cancer population and the continuous optimization of oncolytic virus technology, the market size of China's oncolytic virus drug industry will maintain a compound annual growth rate of 16.2%, and the market size is expected to rise to 1.43 billion yuan by 2024. Project profile Project profile Oncolytic virus is a kind of natural or recombinant virus that can selectively infect and kill tumor cells without damaging normal cells. It can play a synergistic role in combination with chemotherapy, radiotherapy and immunotherapy. The types of viruses studied by oncolytic viruses include adenoviruses, vaccinia viruses, herpes viruses, reovirus and Coxsackie viruses, most of which target refractory solid tumors, including pancreatic cancer, the "king of cancers. The idea of the novel oncolytic virus product targeting strategy is to use the ability of oncolytic virus to specifically target tumor cells, introduce foreign genes (tumor killer genes) into tumor cells, and with the entry of the virus, a large number of killer proteins are expressed, so as to achieve the purpose of killing tumor cells. Oncolytic virus drugs are mainly used in combination immunotherapy, traditional radiotherapy, chemotherapy and other combination drug fields in the future because of their advantages of multi-pathway killing tumor mechanism. The unique design strategy and construction model give the novel oncolytic virus products NR05 and NR06 strong anti-tumor potential, and they are designed to be used as monotherapy or in combination with immune checkpoint inhibitors (PD-1/L1) to treat diseases such as solid tumors and hematologic tumors. Technical introduction NR05 (Ad5-PhTERT-PhSurv-DT) and NR06 (Ad5-PhTERT-PhSurv-RT) are recombinant tumor-killing adenoviruses with a foreign promoter and toxin gene on the genome, and the promoter is located upstream of the toxin gene. To drive its expression in tumor cells and not in normal cells. NR05, NR06 Structure design: (1) Viral vector: Select the most commonly used adenovirus vector HAd5. (2) Vector modification: knockout the adenovirus E1 gene to become a replication-deficient virus, avoiding the interference of the upstream gene of the virus on the expression of toxic proteins, and improving safety. (3) Insertion of tumor-specific tandem promoters: promoters of the human telomerase (PhTERT) and human Survivin(PhSurv) genes are widely used in gene therapy and have the broadest known activity spectrum of cancer types. PhTERT and PhSurv were spliced together to form a novel and efficient tandem promoter. (4) Insertion of natural toxin genes: DT and RT have powerful toxic effects on cells, both of which can inactivate ribosomes, and can achieve the purpose of killing tumor cells or inhibiting tumor growth by expressing toxin proteins in tumor cells through specific promoters. Patent situation 1.The invention discloses a rabies vaccine and a preparation method thereof； 2.New Rabies Vaccine Vector, Rabies Vaccine, Kit Contains the Rabies Vaccine, Method and Kit for Preparation the Rabies Vaccine（Vietnam）； 3.NEW RABIES VACCINE AND METHOD FOR PREPARATION THEREOF（Indonesia）； 4.NEW RABIES VACCINE AND METHOD FOR PREPARATION THEREOF（India）； 5.A culture method for defective adenovirus AdC68-GP。 Team introduction It is composed of internationally renowned virologists, immunologists and senior biological drug development engineers, with a total of more than 200 full-time staff and cooperative teams, of which more than 90% have bachelor's degree or above, and more than 40% have master's degree or above. The core team has more than 15-30 years of related industry experience, and the technical field covers the whole process of biomedical research and development. Established long-term cooperation with Sichuan University, Sichuan Agricultural University and other universities in biotechnology R&D practice and internship employment. 02 Market competitive advantage 01 Design strategy Compared with the current conventional drugs, the transcription targeting strategy of tumor cells using toxin genes is more advantageous for specific targeting of cancer cells. Tumor-specific promoters can be used for this purpose to drive the specific expression of toxins in tumor cells. 02 Targeted and broad spectrum A general-purpose tumor-specific promoter and a strong promoter active in multiple tumor types that can target multiple tumor cells with broad-spectrum anti-tumor potential. 03 effectiveness The introduction of bacterial and plant-derived toxic proteins is different from other therapeutic proteins, and the effect is far more effective than the existing products on the market, and the high activity of the tandem promoter makes the expression of toxic target proteins higher, and thus the lethality of tumor cells is more efficient. 04 security The unique tumor-specific tandem promoter is highly targeted and can treat a wide range of cancers with minimal toxicity. 05 Route of administration It can be injected into the body through intratumoral or intravenous injection, and a variety of administration methods for different tumor types make it more convenient and fast to play a powerful anti-tumor effect. Through rational design, adenovirus genome was optimized and modified to overcome the limitations of other oncolytic viruses and improve their effectiveness and safety by enhancing tumor selective expression. A novel and highly efficient tandem promoter combination, PhTERT-PhSurv, has the highest and more consistent promoter expression levels in different cancer cells. In particular, its average expression level was 4.8 times that of PhTERT, which is widely used in gene therapy, and 3.3 times that of another cancer-specific promoter, PhSurv, which also retained its cancer specificity.
