Anti-signal regulatory protein alpha (hSIRPα) antibody can effectively relieve the inhibition of macrophages by tumor cells. The combinational use of anti-hSIRPα antibody and the immune checkpoint inhibitor anti-hPD-1 antibody could increase efficacy in cancer patients. Creative Biolabs has successfully established an optimized Magic™ “humanized” animal platform to offer specialty manipulated hPD-1/hSIRPα dual humanized mice for our clients all over the world.
The immune system has a complete set of mechanisms to recognize autologous and non-somatic cells, so as to generate immune attacks at the right time, while forming immune tolerance to avoid the occurrence of autoimmune diseases. Human programmed cell death protein-1 (hPD-1) on the surface of T cells is an important protein involved in the above process.
hSIRPα, also termed hCD172a or hSHPS-1, is an inhibitory immunoreceptor belonging to the signal regulatory protein (SIRP) family. In patients with renal cell carcinoma and melanoma, hSIRPα has extremely high expression levels. hSIRPα is a type of immunoglobulin that inhibits the activity of macrophages by binding to hCD47 molecules on the surface of macrophages. However, the anti-hSIRPα antibody can block the inhibition of hSIRPα activity on macrophages by binding to the hCD47 molecule, thereby significantly inhibiting tumor growth.
One of the escape mechanisms of tumors is to suppress the activity of the entire immune system through direct contact, like binding hPD-L1 to hPD-1. hSIRPα is a typical inhibitory immune receptor in the SIRP family, which can be selectively expressed on the surface of myeloid cells and nerve cell membranes. hCD47 is an Ig-like membrane protein widely expressed by various cells and can interact with various cell surface receptors. hSIRPα can be combined with its ligand hCD47 to produce a signal of “don’t eat me”. However, through this mechanism, tumor cells can keep the immune system blind and develop immune evasion. Targeting both hPD-1 and hSIRPα could expose tumor cells under the host immune system, and then activate cytotoxic T cells to kill tumor cells and facilitate the phagocyte by macrophages.
Fig.1 Targets of the SIRPα-CD47 pathway in cancer. (Chao, 2012)
At present, the widely used star drug anti-hPD-1 antibody, when used in combination with anti-hSIRPα antibody, their effects will be significantly enhanced. The combinational use of anti-hPD-1 antibody and anti-hSIRPα antibody may become one of the hotspots in cancer treatment in the future. With advanced technology, Creative Biolabs has multiple well-established Magic™ “humanized” animal models, including the hPD-1/hSIRPα dual humanized mice. Also, we provide the related analysis services for our global clients to advance their drug development. If you have any questions about your study project, please feel free to contact us for further discussions.
Creative Biolabs also offers other various Humanized Mouse Models you may be interested in:
Reference
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