Beauty Tools,Best Beauty Tools,Beauty Care Tools,Hair Straightening Comb Shenzhen Jie Zhong Lian Investment Co., Ltd. , https://www.szmeizon.com
In March 2017, after five patients died of treatment-related cerebral edema, JUNO reluctantly stopped the development of JCAR015 and lost the opportunity to compete with Novartis for the first approved CAR-T treatment product. In May 2017, Kite Pharmaceutical's KTE-C19 showed a patient with multiple organ failure in a safety test, followed by fatal brain edema. Aroused strong market reaction, the stock fell 12% on the day. These messages have raised concerns about the safety of CAR-T therapy.
In the new generation of CAR-T treatment products, large companies are considering adding "switching" technology to the design of CAR-T, such as Bellicum's GoCAR-T and CastaCIDe dual-switch technology, and Intrexon's RheoSwitch technology.
Recently, a company named BioAlta has developed a conditional activation biotechnology technology platform, Conditionally Active Biologics (CAB), which hopes to finally solve the off-target side effects of CAR-T and monoclonal antibody products.
CAB technology principle
The microenvironment between the tumor and normal tissue determines whether these mAbs or CAR-T are activated. Tumor cells can support the rapid expansion of tumor cells by altering the energy metabolism of the cells. Glucose in the cytoplasm is converted to pyruvate by glycolysis, and mitochondria are converted to CO2 and ATP in the presence of oxygen. In the case of anaerobic conditions, pyruvate is primarily converted to lactose, which produces only 6.25% complete glucose metabolism and ATP produced by mitochondrial oxidative phosphorylation. As early as 1990, Otto Warburg reported that in the tumor microenvironment, tumor cells would limit the glycolysis process in a timely manner under aerobic conditions. This metabolic characteristic of tumor cells results in a tumor microenvironment that is different from normal cells. For example, mice transplanted with MCF-7 breast cancer cells create an acidic microenvironment. This condition is also observed in human breast cancer. For some tumors, the acidic environment can increase the invasion and metastasis of the tumor.
In view of the unique innovations of CAB technology, Pfizer signed a $1 billion strategic licensing and options agreement with BioAtla on December 7, 2015, using BioAtla's CAB and Pfizer's ADC technology platform to jointly develop a series of ADC drugs. Increase the safety of ADC drugs. In addition, Pfizer has acquired the global rights to BioAtla's CAB CTLA4 mAb.
Based on the characteristics of the tumor microenvironment, BioAlta scientists optimized a series of CART sequences that have completely different affinities for antigen affinity at different pH values ​​and are activated at different pH values.
In the CAR-T field, BioAtla developed the CCT3 CAB CAR-T series for AXL and ROR3 using the CAB platform. The fourth-generation bedside CAR-T CCT4 was also developed in conjunction with F1 oncology, which took only 4 hours to complete, realizing bedside CAR-T treatment.
BioAtla's CAB technology is especially suitable for the treatment of solid tumors. If combined with immunological checkpoint inhibitors such as PD1, it is very likely to achieve good clinical results. At present, CART CCT3 and CCT4's Greater China rights are owned by a domestic company named Xuxi Bio, and are currently in clinical trials before entering the human trial phase.
Activate the biopharmaceutical drug giant or add a "switch" to CAR-T
[ China Pharmaceutical Network Technology News ] CAR-T, the full name is Chimeric Antigen Receptor T-Cell Immunotherapy, chimeric antigen receptor T cell immunotherapy. This is a new type of cell therapy that has been around for many years, but has been improved and used clinically in recent years. In the new generation of CAR-T treatment products, many pharmaceutical giants have considered adding "switching" technology to the design of CAR-T.
(Activate the biopharmaceutical drug giant or add a "switch" to CAR-T)