The team from the National Institutes of Health and the Academia Sinica published new results in the development of cancer drugs.
(provided by the National Health Service)
[Reporter Lin Huiqin/Taipei Report] A protein CD47, which is widely expressed on the surface of cancer cells, can bind to the signal regulatory protein α (SIRPα) on the surface of human macrophages to convey the signal of "don't eat me" to macrophages. Cancer cells can escape the defense of the immune system, and the therapeutic effect is reduced. However, the National Institutes of Health and the Academia Sinica have cooperated to design an oral small molecule isoQC inhibitor, which can interrupt the transmission of the "don't eat me" signal. It has been confirmed that the combination of monoclonal antibodies can improve the efficacy, and it is expected to enter the first phase of clinical trials in 1 to 2 years at the earliest.
Chen Zhihao, an associate researcher at the Institute of Biotechnology and Medicine of the National Institutes of Health, said that monoclonal antibodies have limited efficacy. Past studies have found that they are related to a protein CD47 located on the cell surface, which is widely expressed on the surface of various cancer cells and can interact with SIRPα on the surface of macrophages. Combined, the "don't eat me" signal to macrophages is thought to be a key for cancer cells to evade the immune system.
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Chen Zhihao pointed out that "glutamic acid amine cyclization isoenzyme" (isoQC) is an important regulator of the binding of CD47 to SIRPα. Therefore, by regulating the role of isoQC, it is expected to enhance the phagocytosis of cancer cells by macrophages.
Yan Wanjing, a researcher at the Institute of Biotechnology and Medicine of the National Institutes of Health, pointed out that the Institute of Biotechnology and Medicine of the National Institutes of Health and the Institute of Biochemistry of the Chinese Academy of Sciences jointly formed a new drug research and development team. Using the CD47-SIRPα axis as a target, they successfully developed a small molecule isoQC inhibitor for oral use. It can effectively inhibit the enzymatic activity of isoQC, thereby reducing the combination of CD47 and SIRPα on the surface of tumor cells, and enhancing the phagocytosis of cancer cells by macrophages, thereby achieving the effect of cancer treatment.
Yan Wanjing pointed out that, through animal experiments, it was found that using monoclonal antibody combined with isoQC inhibitor to treat head and neck cancer and lymphoma, about 50% of mouse tumors disappeared within 30 days of treatment, and 75% did not recur within 150 days, which is higher than that of using monoclonal antibody alone. 38% of mice treated with monoclonal antibody did not relapse during the same period, showing that the efficacy of monoclonal antibody can be enhanced with isoQC inhibitor.
Zhang Junyan, director of the Institute of Biotechnology and Drugs of the National Institutes of Health, said that isoQC inhibitors can be used in combination with chemotherapy, monoclonal antibodies, and even immunotherapy, but the current drug still needs to undergo preclinical toxicology tests, which are expected to be available in the fastest 1 to 2 years. Entered Phase 1 clinical trial.
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head and neck cancer