动物造模,人源化动物模型 z-bio 2021-10-22 710

　　Preclinical research is the main challenge

　　Problems faced by major R&D institutions, such as the clinical efficacy of new drugs and the risks and benefits of time costs. From preclinical research to clinical research to final CFDA/FDA approval, modern drug development takes a long time and is very expensive, and the possibility of eventual failure is very high. In the development of new drugs, we always have to face various difficulties, and all connections are very important.

　　The R&D process needs to go through many steps, such as drug design and screening, chemical synthesis and modification, pharmacy and pharmacokinetic research, process and preparation, quality testing and control, safety and clinical evaluation, market feedback, etc.

　　According to the work content, new drug research and development can be divided into four stages: discovery/screening, preclinical research, clinical research, new drug declaration and follow-up. First, discovery and screening include basic and applied research (including drug preparation and preliminary screening) and drug source discovery and screening. Subsequent clinical trials include phase I (preliminary clinical pharmacology studies, human safety studies), phase II (preliminary evaluation of therapeutic effects, safety studies), phase III clinical studies and preparations (extended clinical studies, special studies). Clinical trials, supplementary clinical trials, observing side effects). Finally, the new drug application and follow-up work includes the new drug application and other work required by the CFDA (U.S. Food and Drug Administration) to review the new drug application.

　　For companies and researchers, clinical research requires high costs. If the test fails, not only will the drug research be in trouble, but also a lot of money will be lost. For cancer patients, participating in clinical trials of certain new drugs is usually their last hope, that is, if the trial fails, it will have a greater impact on patients and their families.

　　Pre-clinical research is the first challenge in drug development. Preclinical research refers to the chemical synthesis or natural product purification research conducted before the drug enters the clinical research, drug analysis research, pharmacodynamics, pharmacokinetics, toxicology and pharmacology research. Every year, a large number of new drugs are eliminated in the phase I clinical process. After all, there is a huge difference between animal experiments and human experiments.

　　Whether it is for veterinary or human drug development, animal models are used to study disease treatment methods and animal studies to verify the safety and effectiveness of new drugs. For many researchers, what drugs can participate in clinical trials is a headache. Regarding tumor immunity (CAR-T/Checkpoint), its mechanism of action is to mobilize and kill autoimmunity, which is different from the mechanism of action of conventional target drugs. Therefore, we need a model to simulate the immune environment of the human body in the preclinical stage. A good preclinical evaluation system can provide very valuable and meaningful test data for reference, such as the use of humanized mouse models to evaluate new drugs.

　　Valuable tool—humanized mouse model

　　Because the physiology of humans and animals are very different, the experimental results obtained using animal models may not be applicable to humans. Human tumor tissue xenografts (patient-derived xenografts, PDX) mouse models can be used to evaluate the safety and efficacy of new human-related drugs in animals, and to simulate human clinical trials. Taking into account the particularity of tumor immunotherapy, Edmore independently developed a mouse HSC model suitable for evaluating tumor immunotherapy. This model can reshape the mouse immune system by transplanting artificial hematopoietic stem cells and transplanting human tumor tissue on the basis of it. This not only improves the acceptance rate of pharmaceutical companies to drugs, but also increases the rate of tumor acquisition, thereby gaining immunity Dual source mouse model. It provides clinical trials to help patients find the most suitable treatment options, and provides powerful tools for the preclinical evaluation of the human immune system and cell-mediated immunotherapy. Dr. Peng Siying, CEO and founder of Beijing Idemo Biotechnology Co., Ltd., said that humanized immune reconstruction mice accelerate the development of new drugs and effectively shorten the clinical trial cycle of new drugs. They are innovative drugs in China and costly. And accelerate the emergence of clinical trial risks of new therapies.

　　The future market is vast

　　The global anti-cancer drug market in 2011 was approximately US$83 billion. In the past five years, the global anti-cancer drug market has grown at a compound annual growth rate of 7.6%, which is the 4.3% compound annual growth rate of the global pharmaceutical market. The size of the anti-tumor drug market in my country is about 80 billion yuan, with an average annual compound growth rate of about 20%. In 2012, the market share of anti-tumor and immunosuppressive drugs surpassed 16.46% of antibiotics and entered the market, making it the largest prescription drug category in the country.

　　The huge demand for new drug research and development has also brought a broad market for humanized mouse drug evaluation models. According to Ames research data, in the past five years, 70 new drugs have emerged to treat more than 20 tumor diseases. Currently, more than 586 anti-cancer drugs are being studied, an increase of 63% in the past ten years, of which 87% are targeted.

　　The advancement of science and technology has led to the development of medicine. In the face of sick patients, there are more choices, and new oncology drugs continue to emerge. According to AMS data, there are currently more than 586 kinds of oncology drugs under development. In the past ten years, it has grown by 63%, with targeted drugs accounting for 87%. Advanced tumor therapy includes 270 biological therapies, including 16 gene therapies, 86 new monoclonal antibodies and 15 biological analogs of monoclonal antibodies that have been on the market. Late-stage products also include 74 cancer vaccines for multiple tumor types.

　　China Industrial Research Network released a research analysis and development trend forecast report on China's anticancer drug industry from 2016 to 2022. The "BRIC countries" of China, India, Brazil and Russia are the fastest growing anticancer drugs in the world. Will be on the market. In China, due to the rapid growth of tumor incidence, the development prospects of the anti-tumor drug market are very broad. At the same time, due to the current limitations of drug efficacy, the new anti-tumor drug market is developing rapidly. There is an urgent need for active development. popular. The rapid development of oncology drug research and development will further promote the development of humanized mouse drug evaluation models.