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Bispecific fibrous glue synergistically boosts vascular normalization and antitumor immunity for advanced renal carcinoma therapy.
- 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.)
- Subjects :
- Animals
Humans
Mice
Cell Line, Tumor
Tumor Microenvironment drug effects
Mice, Inbred BALB C
Female
B7-H1 Antigen antagonists & inhibitors
B7-H1 Antigen metabolism
Kidney Neoplasms pathology
Kidney Neoplasms drug therapy
Kidney Neoplasms therapy
Kidney Neoplasms immunology
Carcinoma, Renal Cell pathology
Carcinoma, Renal Cell immunology
Carcinoma, Renal Cell therapy
Carcinoma, Renal Cell drug therapy
Subjects
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