Hengrui announced at the end of last month that it had received the Drug Clinical Trial Approval issued by the State Drug Administration of China (SDA) and would conduct Phase I clinical trial soon. The basic information of the pharmaceutical product is as follows:
|
Pharmaceutical product name |
SHR-1603 Injection |
|
Dosage form |
Injection |
|
Specification |
2ml:0.1g |
|
Application matter |
Registration of Chinese-produced pharmaceutical product |
|
Registration classification |
Biological product for treatment |
|
Applicant |
Jiangsu Hengrui Medicine Co., Ltd., Shanghai Hengrui Pharmaceutical Co., Ltd., and Suzhou Suncadia Biopharmaceuticals Co., Ltd. |
|
Acceptance No. |
CXSL1800011 |
|
Approval No. |
2018L02559 |
(Source: Eastmoney.com)
The Chinese R&D giant Hengrui has kept this pharmaceutical product in strict confidence, which only has a code and does not provide any information about the target, therefore, this news did not cause much backlash in the industry at that time. However, I’ve learned from an insider recently that SHR-1603 actually targets the very hot oncology target CD47 in recent two years. You don’t know what CD47 is? Let me analyze it below.
Anti-CD47 antibody—the next star in the tumor immunotherapy field
CD47 is also known as integrin associated protein (IAP) that belongs to the immunoglobulin superfamily; the protein is a five transmembrane protein, with molecular weight of about 50kDa, and extracellular N-terminal of IgG4 domains. CD47 is an important marker of "self" on the cell surface and an important signal regulating the phagocytosis of macrophages; it can bind to SIRPα on the surface of macrophages and phosphorylate the ITIM thereof, and then recruit SHP-1 protein, to produce a series of cascade reactions to inhibit the phagocytosis of macrophages.
CD47 is extensively expressed on the surface of many healthy cells and releases "Don't eat me" signal to macrophages, thus to protect healthy cells from damaging by the immune system. When cells age or have cytopathy, cell surfaces will gradually lose CD47 to help the body identify and deal with those cells. Unfortunately, this mechanism is used by the cancer cells which, in order to protect themselves, arrange more CD47 on their surface than normal cells have, and as CD47 binds to SIRPα, the "Don't eat me" is also released, resulting in the macrophages not to swallow the cancer cells.
There are currently two theories regarding the mechanism of action of anti-CD47 antibodies:
One is that cancer cells up-regulate expression of CD47 to fool macrophages, while anti-CD47 antibodies enable macrophage to bring into play the phagocytosis by blocking "Don't eat me" signal. For this mechanism, Stanford University Dr. Weissman, Founder of Forty Seven, has conducted a series of work for demonstration, as shown in the following figure:
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