Tumor metastasis is a complex process that results in the leading cause of cancer-related death. It is triggered by a subpopulation of circulating tumor cells (CTCs). It is well-known that the host immune system generally serves as a barrier against multiple tumor formation and metastasis. Programmed death-ligand 1 (PD-L1) transmits the "don't find me" signal to the adaptive immune system, while CD47 transmits the "don't eat me" signal to the innate immune system. As both PD-L1 and CD47 are overexpressed on human tumors, dual targeting innate and adaptive immune checkpoints would present better anti-tumor therapeutic effects and more durable responses. In the meantime, it would be a promising solution to avoid the problems of single antibody limitation, fewer checkpoints, and poor targeting.
There has been a phage-derived human IgG1 antibody targeting PD-L1 approved in 2016. An engineered SIRPα variant with a high affinity to CD47are designed by researchers. Researchers constructed an innate and adaptive immunity-dependent bispecific fusion protein using the variable region of the PD-L1 mAb and engineered SIRPα variant in an IgG1 backbone. Clinical trials certificated that compared with systemic administration, the dual-targeting fusion protein format would generate better anti-tumor effects with fewer side effects.
The bispecific antibodies (bsAb) construct of anti-CD47 and anti-PD-L1 mAb remained to block activity for both interactions but lacked the hemagglutinating activity. The CD47 binding affinity was reduced, but the PD-L1 binding affinity is comparable to anti-PD-L1 mAb. Besides, there is another bsAb against PD-L1 and CD47 in phase 1 trials for advanced tumor treatment.
Creative Biolabs is a leading service provider that focuses on combined therapy against multiple cancers. Based on our advanced drug discovery platform and extensive experience, now Creative Biolabs helps for combined therapy research of PD-1 and CD47 against multiple cancers for our clients all over the world; the services we provide include but not limited to:
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