Journal
ISCIENCE
Volume 24, Issue 2, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.isci.2021.102104
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Funding
- Basic Science Research Program through the National Research Foundation of Korea (NRF) [2019R1I1A3A01047208, 2019R1I1A1A01058773]
- Regional Leading Research Center through the National Research Foundation of Korea (NRF) [2020R1A5A8019180]
- Korea Basic Science Institute [D010730]
- National Research Facilities & Equipment Center [2019R1A6C1010006]
- 2018 Research Grant from Kangwon National University [520180060]
- Korean government (Ministry of Education and Ministry of Science and ICT)
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The study investigates the influence of protein binding affinity on tumor localization, highlighting the importance of optimal affinity for deep penetration into tumors. The debate over establishing a relationship between binding affinity and tumor localization still exists.
Systematic control of in vivo behavior of protein-based therapeutics is considered highly desirable for improving their clinical outcomes. Modulation of biochemical properties including molecular weight, surface charge, and binding affinity has thus been suggested to enhance their therapeutic effects. However, establishing a relationship between the binding affinity and tumor localization remains a debated issue. Here we investigate the influence of the binding affinity of proteins on tumor localization by using four repebodies having different affinities to EGFR. Biochemical analysis and molecular imaging provided direct evidence that optimal affinity with balanced target binding and dissociation can facilitate deep penetration and accumulation of protein binders in tumors by overcoming the binding-site-barrier effect. Our findings suggest that binding kinetics-based protein design can be implicated in the development of fine-tuned protein therapeutics for cancers.
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