The dawn of immunotherapy! National Health Research Institutes of Taiwan develops new "attack macrophage" drugs: cancer cells are "mercilessly engulfed" when they see them
It is expected to become a new treatment option for “multiple cancers”! National Health Research Institutes of Taiwan joins hands with Taiwan Academia Sinica to develop new oral drugs
Cancer has been one of the top ten causes of death in Taiwan for 40 years. The cancer rate among Taiwanese people has been rising year by year. Traditional surgical treatment can only treat patients with localized tumors. Chemotherapy and radiotherapy come with many adverse side effects. Cancer cells suffer from persistent genetic changes. Mutations produce drug resistance and change the tumor microenvironment to escape immune system surveillance, thereby compromising the effectiveness of targeted therapy.
In recent years, research on the internal and external immune mechanisms of normal cells and cancer cells has become increasingly clear. Immunotherapy, which uses the adjustment of the tumor microenvironment to strengthen the immune system and thereby eliminate cancer cells, is currently a more targeted and effective emerging therapy for the treatment of cancer.
A new drug research and development team jointly formed by the National Institute of Biotechnology and Pharmaceutical Sciences of the National Institutes of Health and the Institute of Biochemistry of Academia Sinica successfully developed a new type of potent oral small molecule isoQC inhibitor using “CD47-SIRP α axis” as a target. , this new type of isoQC inhibitor can effectively inhibit the enzyme activity of isoQC, thereby reducing the binding of CD47 and SIRPα on the surface of tumor cells, enhancing the phagocytosis of cancer cells by macrophages, thereby achieving the effect of treating cancer. It is suitable for a variety of Oral drug candidates for cancer immunotherapy.
Prevent cancer cells from sending “Don’t eat me” signals “isoQC” inhibitor regulates macrophage function
The National Health Research Institutes of Taiwan team pointed out that CD47 is a protein located on the cell surface and is widely expressed in normal cells and cancer cells. When CD47 binds to Signal regulatory protein α (SIRPα) on the surface of macrophages, It will convey the “don’t eat me” signal to macrophages and serve as an immune checkpoint to inhibit macrophage phagocytosis.
Past studies have found that CD47 is widely expressed on the surface of various cancer cells, so it is also considered to be a key for cancer cells to evade the immune system. Glutaminyl cyclase isoenzyme (isoQC) is an important regulator of the binding between CD47 and SIRPα. Therefore, by regulating the function of isoQC, the phagocytosis of cancer cells by macrophages can be regulated.
DBPR22998 is an oral small molecule isoQC inhibitor developed by the National Health Research Institutes of Taiwan R&D team. It has been proven to have a strong inhibitory effect on isoQC and can effectively inhibit a variety of tumor cell lines with high CD47 expression. Interaction of CD47 with SIRα-Fc protein. In addition, antibody-dependent cellular phagocytosis was confirmed in human macrophages. In different solid tumor and blood tumor animal model experiments, it was confirmed that the combination of DBPR22998 and therapeutic antibodies can effectively enhance the anti-tumor efficacy.
No side effects of inhibiting red blood cells and platelets! Research team reveals “3 major advantages” of new oral drugs
There are currently cancer treatments using CD47 monoclonal antibodies. However, CD47 monoclonal antibodies bind to normal cells, so a high dose is required to inhibit tumor cells. However, high doses of CD47 monoclonal antibodies will inhibit “Don’t eat” on red blood cells. “I” signal prompts macrophages to engulf red blood cells and cause anemia.
The National Health Research Institutes of Taiwan team further pointed out that small molecule isoQC inhibitors will not cause red blood cell reduction or thrombocytopenia. Therefore, these drugs avoid the potential side effects and risks of CD47 monoclonal antibody treatment, and are more suitable for cancer immunotherapy. safety. In addition, isoQC inhibitors can be made into oral drugs, and the manufacturing method is relatively simple and low-cost.
DBPR22998 is the first novel, oral small molecule drug candidate in the field of cancer immunotherapy. It is suitable for the treatment of a variety of cancers. In addition to promoting the phagocytosis effect of macrophages to phagocytose tumors and increasing the effect of cancer treatment, it has also prolonged the efficacy of cancer treatment in animal experiments. The overall average survival time of mice with tumors and low side effects. Used in combination with monoclonal antibody-targeted drugs or immune checkpoint antibody drugs, it can treat cancer patients who are prone to relapse and have high drug resistance.
The National Health Research Institutes of Taiwan team stated that DBPR22998 has received patent approval from the United States, Taiwan, Japan, South Korea, China and Australia. The current research on DBPR22998 is still in the pre-clinical stage and looks forward to working with them. The biotechnology industry in Taiwan and abroad carries out technology transfer or industry-university cooperation to jointly promote clinical trials, thereby driving the growth and international competitiveness of the new biotechnology drug industry.
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