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Int. J. Mol. Sci. 2018, 19(5), 1435; https://doi.org/10.3390/ijms19051435

High Affinity Promotes Internalization of Engineered Antibodies Targeting FGFR1

1
Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, Joliot-Curie 14a, 50-383 Wroclaw, Poland
2
Department of Protein Biotechnology, Faculty of Biotechnology, University of Wroclaw, Joliot-Curie 14a, 50-383 Wroclaw, Poland
*
Authors to whom correspondence should be addressed.
Received: 15 April 2018 / Revised: 29 April 2018 / Accepted: 8 May 2018 / Published: 10 May 2018
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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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 antibody displays fastest internalization kinetics. Our data may facilitate design of therapeutically relevant targeting molecules for selective treatment of FGFR1 overproducing cancers. View Full-Text
Keywords: affinity; cancer therapy; engineered antibodies; FGFR1; internalization affinity; cancer therapy; engineered antibodies; FGFR1; internalization
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Opaliński, Ł.; Szymczyk, J.; Szczepara, M.; Kucińska, M.; Krowarsch, D.; Zakrzewska, M.; Otlewski, J. High Affinity Promotes Internalization of Engineered Antibodies Targeting FGFR1. Int. J. Mol. Sci. 2018, 19, 1435.

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