High Affinity Promotes Internalization of Engineered Antibodies Targeting FGFR1

International Journal of Molecular Sciences
Łukasz OpalińskiJacek Otlewski

Abstract

Fibroblast growth factor receptor 1 (FGFR1) is a plasma membrane protein that transmits signals from the extracellular environment, regulating cell homeostasis and function. Dysregulation of FGFR1 leads to the development of human cancers and noncancerous diseases. Numerous tumors overproduce FGFR1, making this receptor a perspective target for cancer therapies. Antibody-drug conjugates (ADCs) are highly potent and selective anticancer agents. ADCs are composed of antibodies (targeting factors) fused to highly cytotoxic drugs (warheads). The efficiency of ADC strategy largely depends on the internalization of cytotoxic conjugate into cancer cells. Here, we have studied an interplay between affinity of anti-FGFR1 antibodies and efficiency of their cellular uptake. We have developed a unique set of engineered anti-FGFR1 antibodies that bind the same epitope in the extracellular part of FGFR1, but with different affinities. We have demonstrated that these antibodies are effectively taken up by cancer cells in the FGFR1-dependent manner. Interestingly, we have found that efficiency, defined as rate and level of antibody internalization, largely depends on the affinity of engineered antibodies towards FGFR1, as high affinity antibod...Continue Reading

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Citations

Dec 24, 2018·Journal of Clinical Medicine·Natalia PorębskaŁukasz Opaliński
Jun 3, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Calvin D LewisVaishali Kapoor
Jul 28, 2020·Photodiagnosis and Photodynamic Therapy·Kohei Nakajima, Mikako Ogawa
Dec 3, 2021·Biomacromolecules·Natalia PorębskaŁukasz Opaliński

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Methods Mentioned

BETA
phage display
surface plasmon resonance
pull down
fluorescence microscopy
ELISA

Software Mentioned

ImageJ
ZEN
BIAevaluation

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