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 by contrivance of a PEG4 linker. This make made this peptide proof towards serum proteolysis and gathered in the tumor tissues. It could perhaps block CD47/SIRPα and PD-1/PD-L1 to toughen the phagocytosis of macrophage, and block PD-1/PD-L1 to restore the design of T cell. Credit score: ©Science China Press
Professor Yanfeng Gao’s crew from the School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University possess designed and synthesized Pal-DMPOP, a chimeric peptide that can perhaps simultaneously block CD47/SIRPα and PD-1/PD-L1. This bispecific peptide elicits synergistic antitumor activity by bettering 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 successfully suggested antitumor immunity in a technique of tumor forms, easiest a small subset of sufferers can clutch pleasure in PD-1/PD-L1 blockade. CD47 expressed on tumor cells protects them from phagocytosis by contrivance of interaction with SIRPα on macrophages, whereas PD-L1 dampens T cell-mediated tumor killing.
Also, it became once reported that macrophages can additionally suppose PD-1 to mediate a “make no longer exhaust me” stamp by contrivance of interaction with PD-L1 on tumor cells. When compared with antibodies, peptides possess better tumor penetration ability and straightforward to be synthesized. Ensuing from this truth, make of peptides dual-focusing on blockade of each PD-1/PD-L1 and CD47/SIRPα might perhaps toughen the efficacy of most cancers immunotherapy.
Pal-DMPOP (1 mg/kg, i.p., on every day basis) seriously inhibits the tumor progress (A), has no impact on body weights (B), enhances CD8+ T cell infiltration (C) and its IFN-γ secretion in the tumor tissue (D). The infiltration of intratumoral macrophages (CD45+CD11b+F480+) (E) and the M1/M2 ratio (F) in the tumor tissue had been elevated. Credit score: ©Science China Press
On this text, the authors designed a chimeric peptide Pal-DMPOP. It consists of the smallest fragment of the D-peptide inhibitor of PD-1/PD-L1 (OPBP-1) and the optimized peptide inhibitor of CD47/SIRPα (Pep-20). Also, the palmitic acid tail became once modified at its N-terminal to toughen its anti-enzymatic ability and in vivo half-lifestyles.
The research crew verified that Pal-DMPOP can toughen the phagocytosis of macrophages on tumor cells, and can additionally restore the killing attain of CD8+T cells on tumor cells in vitro. The attain of tumor immunotherapy in vivo has been certain in MC38 and CT26 mouse devices. The tumor quantity in Pal-DMPOP administration community is seriously reduced compared with the alter community, and Pal-DMPOP has no obvious toxic attain in the tumor-bearing mice.
More info:
Zheng Hu et al, Carry out of a original chimeric peptide by contrivance of dual blockade of CD47/SIRPα and PD-1/PD-L1 for most cancers immunotherapy, Science China Life Sciences (2023). DOI: 10.1007/s11427-022-2285-6
Citation:
Researchers synthesize chimeric peptide that elicits antitumor activity for most cancers immunotherapy (2023, June 30)
retrieved 3 July 2023
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