Engineering a Smart Agent for Enhanced Immunotherapy Effect by Simultaneously Blocking PD‐L1 and CTLA‐4

Combinations of immune checkpoint therapies show encouraging results in the treatment of many human cancers. However, the higher costs and greater side effects of such combinations compared with single‐agent immunotherapies limit their further applications. In this work, a novel smart agent, KN046@1...

Full description

Saved in:
Bibliographic Details
Published in:Advanced science Vol. 8; no. 20; pp. e2102500 - n/a
Main Authors: Jiang, Chunjuan, Zhang, Le, Xu, Xiaoping, Qi, Ming, Zhang, Jianping, He, Simin, Tian, Qiwei, Song, Shaoli
Format: Journal Article
Language:English
Published: Germany John Wiley & Sons, Inc 01.10.2021
John Wiley and Sons Inc
Wiley
Subjects:
19F MRI
Animals
Antibodies
Antibodies, Bispecific - chemistry
Antibodies, Bispecific - immunology
Antibodies, Bispecific - pharmacology
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
B7-H1 Antigen - antagonists & inhibitors
B7-H1 Antigen - genetics
B7-H1 Antigen - immunology
Cancer
Cell Line, Tumor
Cell Proliferation - drug effects
CTLA-4 Antigen - antagonists & inhibitors
CTLA-4 Antigen - genetics
CTLA-4 Antigen - immunology
Efficiency
FDA approval
Fluorine
granzyme B probes
Humans
Immune Checkpoint Inhibitors - pharmacology
immunotherapies
Immunotherapy
Melanoma
Mice
Nanoparticles
Neoplasms - genetics
Neoplasms - immunology
Neoplasms - therapy
Physiology
positron emission tomography/computed tomography imaging
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - immunology
Recombinant Fusion Proteins - pharmacology
Scanning electron microscopy
Single-Domain Antibodies - chemistry
Single-Domain Antibodies - immunology
Single-Domain Antibodies - pharmacology
Tumors
Xenograft Model Antitumor Assays
ZIF‐8
immunotherapies
granzyme B probes
positron emission tomography/computed tomography imaging
ZIF-8
19F MRI
ISSN:2198-3844, 2198-3844
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Combinations of immune checkpoint therapies show encouraging results in the treatment of many human cancers. However, the higher costs and greater side effects of such combinations compared with single‐agent immunotherapies limit their further applications. In this work, a novel smart agent, KN046@19F‐ZIF‐8, is developed to overcome these limitations. KN046 is a novel recombinant humanized PD‐L1/CTLA‐4 bispecific single‐domain antibody‐Fc fusion protein, which can bind to both PD‐L1 and CTLA‐4 effectively. ZIF‐8 is a smart delivery system, which can safely and effectively deliver KN406 to a tumor. In vitro and in vivo results demonstrate that the smart agent KN046@19F‐ZIF‐8 not only improves the immune response rate of the antibody drug in treatment of tumors but also reduces its toxic side effects, thereby achieving excellent antitumor efficacy. This study provides an engineering strategy for clinical applications of a more effective immunotherapy. A novel smart agent is engineered by coating a tumor microenvironment responsive ZIF‐8 on the novel recombinant humanized PD‐L1/CTLA‐4 bispecific single‐domain antibody‐Fc fusion protein to overcome the higher costs and greater side effects of single‐agent immunotherapies.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ISSN:2198-3844
2198-3844
DOI:10.1002/advs.202102500