Researchers synthesize chimeric peptide that elicits antitumor activity for cancer immunotherapy

No
Redakcija
-
Researchers synthesize chimeric peptide that elicits antitumor activity for cancer immunotherapy
The peptide Pal-DMPOP consists a peptide inhibitor of CD47/SIRPα, a D-peptide inhibitor of PD-1/PD-L1, and a palmitic acid tail conjugated at its N-terminal through a PEG4 linker. This design made this peptide resistant to serum proteolysis and accumulated in the tumor tissues. It can block CD47/SIRPα and PD-1/PD-L1 to enhance the phagocytosis of macrophage, and block PD-1/PD-L1 to restore the function of T cell. Credit: ©Science China Press

Professor Yanfeng Gao’s team from the School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University have designed and synthesized Pal-DMPOP, a chimeric peptide that can simultaneously block CD47/SIRPα and PD-1/PD-L1. This bispecific peptide elicits synergistic antitumor activity by enhancing macrophages phagocytosis and activating CD8+ T cells. The findings are published in the journal Science China Life Sciences.

Although immune checkpoint inhibition has been shown to effectively activate antitumor immunity in various types, only a small subset of patients can benefit from PD-1/PD-L1 blockade. CD47 expressed on protects them from phagocytosis through interaction with SIRPα on macrophages, while PD-L1 dampens T cell-mediated tumor killing.

Also, it was reported that macrophages can also express PD-1 to mediate a “don’t eat me” signal through interaction with PD-L1 on tumor cells. Compared with antibodies, peptides have better tumor penetration ability and easy to be synthesized. Therefore, design of peptides dual-targeting blockade of both PD-1/PD-L1 and CD47/SIRPα may improve the efficacy of cancer immunotherapy.

Read More

Zaļā Josta - Reklāma