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Bispecific fibrous glue synergistically boosts vascular normalization and antitumor immunity for advanced renal carcinoma therapy.

Authors :
Wu XH
Wang JQ
Wang MD
Xiao T
Wang Y
Niu JY
Wang L
Hou DY
Fu B
Liu Z
Wang H
Xu W
Source :
Biomaterials [Biomaterials] 2024 Jul; Vol. 308, pp. 122550. Date of Electronic Publication: 2024 Mar 28.
Publication Year :
2024

Abstract

Immune checkpoint blockade therapy represented by programmed cell death ligand 1 (PD-L1) inhibitor for advanced renal carcinoma with an objective response rate (ORR) in patients is less than 20%. It is attributed to abundant tumoral vasculature with abnormal structure limiting effector T cell infiltration and drug penetration. We propose a bispecific fibrous glue (BFG) to regulate tumor immune and vascular microenvironments simultaneously. The bispecific precursor glue peptide-1 (pre-GP1) can penetrate tumor tissue deeply and self-assemble into BFG in the presence of neuropilin-1 (NRP-1) and PD-L1. The resultant fibrous glue is capable of normalizing tumoral vasculature as well as restricting immune escape. The pre-GP1 retains a 6-fold higher penetration depth than that of antibody in the multicellular spheroids (MCSs) model. It also shows remarkable tumor growth inhibition (TGI) from 19% to 61% in a murine advanced large tumor model compared to the clinical combination therapy. In addition, in the orthotopic renal tumor preclinical model, the lung metastatic nodules are reduced by 64% compared to the clinically used combination. This pre-GP1 provides a promising strategy to control the progression and metastasis of advanced renal carcinoma.<br />Competing Interests: Declaration of competing interest The authors declare that they have no competing interests.<br /> (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Details

Language :
English
ISSN :
1878-5905
Volume :
308
Database :
MEDLINE
Journal :
Biomaterials
Publication Type :
Academic Journal
Accession number :
38581762
Full Text :
https://doi.org/10.1016/j.biomaterials.2024.122550