Dual function antibody targeting αvβ3 and PD-L1 provide a promising strategy for solid tumor therapy

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Cancer immunotherapy using PD-1/PD-L1 axis inhibitors shows promise but has limitations.
• Integrin αvβ3 is implicated in PD-L1 expression and cancer immune evasion.
• Targeting both PD-L1 and αvβ3 may overcome limitations of current immunotherapies.

Purpose of the Study:

• To investigate the correlation between PD-L1 and αvβ3 expression in solid tumors.
• To develop and evaluate a dual-function antibody (B1451) targeting both PD-L1 and αvβ3.
• To assess the antitumor efficacy of B1451 in preclinical cancer models.

Main Methods:

• Analysis of TISIDB database for PD-L1 and αvβ3 expression correlation.
• Design and construction of a dual-function antibody (B1451) by conjugating an αvβ3-binding peptide to an anti-PD-L1 antibody.
• In vitro and in vivo evaluation of B1451's antitumor efficacy in preclinical models.

Main Results:

• A significant positive correlation was observed between PD-L1 and αvβ3 gene expression in human solid tumors.
• The dual-function antibody B1451 effectively recognized and blocked both PD-L1 and αvβ3 pathways.
• B1451 demonstrated potent inhibition of tumor cell migration, adhesion, and angiogenesis in vitro, with superior antitumor activity in vivo compared to monotherapy.

Conclusions:

• Dual-function antibodies targeting αvβ3 and PD-L1 can reverse immune evasion.
• B1451 exhibits synergistic antitumor effects, presenting a promising therapeutic strategy for solid tumors.
• This approach holds potential for improving patient outcomes in cancer immunotherapy.