Journal
ADVANCED SCIENCE
Volume 8, Issue 20, Pages -Publisher
WILEY
DOI: 10.1002/advs.202102500
Keywords
F-19 MRI; granzyme B probes; immunotherapies; positron emission tomography/computed tomography imaging; ZIF-8
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Funding
- National Natural Science Foundation of China [81771861, 81971648]
- Shanghai Scientific and Technological Innovation Program [19142202100]
- Science and Technology Development Fund of Shanghai Pudong New Area [PKJ2020-Y55]
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The development of a novel smart agent KN046@F-19-ZIF-8 improves the immune response rate of antibody drugs in tumor treatment and reduces toxic side effects, achieving excellent antitumor efficacy.
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@F-19-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@F-19-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.
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