Anticancer activity and antibody-dependent cell-mediated cytotoxicity of novel anti-nucleolin antibodies

Scientific Reports
Sofia RomanoJoão Gonçalves

Abstract

Nucleolin arises as a relevant target for cancer therapy, as it is overexpressed at the surface of cancer and angiogenic endothelial cells thus enabling a dual cellular targeting strategy. Immunotherapeutic strategies, albeit of proven therapeutic relevance, have been scarcely explored against this target. Therefore, this work aimed at engineering an anti-nucleolin VHH-based antibody capable of triggering anticancer immune responses. Herein, anti-nucleolin VHHs have been generated upon grafting F3 peptide-derived nucleolin-binding sequences onto a VHH CDR1 or CDR3. One of these nucleolin-binding CDR3-grafted VHH was subsequently fused to a human IgG1 Fc region, enabling a significant antibody-dependent cell-mediated cytotoxicity (ADCC). The generated anti-nucleolin VHH revealed increased binding and antiproliferative effects against cancer cells, relative to the parental VHH, while the VHH-Fc counterpart presented increased cytotoxicity relative to the corresponding VHH. This VHH-Fc also triggered an ADCC effect, in the nanomolar range, against a nucleolin-overexpressing cancer cell line. This effect was evidenced by a 2 or 1.7-fold increase of cell death, in the presence of PBMCs, relative to the parental VHH-Fc or the VHH cou...Continue Reading

References

Jun 19, 1989·FEBS Letters·M SrivastavaA L Burns
Apr 1, 1973·Virology·F L Graham, A J van der Eb
Nov 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·C F BarbasJ W Smith
Jun 3, 1993·Nature·C Hamers-CastermanR Hamers
Jan 1, 1996·Molecular Biology Reports·J S DengJ K Hofmeister
Jul 3, 1998·The EMBO Journal·M LauwereysS Muyldermans
Dec 9, 2000·Experimental Cell Research·A G HovanessianB Krust
May 29, 2002·Proceedings of the National Academy of Sciences of the United States of America·Kimmo PorkkaErkki Ruoslahti
Jun 5, 2003·Nature Reviews. Cancer·Gabriele Bergers, Laura E Benjamin
Aug 2, 2003·Breast Cancer Research and Treatment·Angelos D GritzapisMichael Papamichail
Aug 13, 2004·Proceedings of the National Academy of Sciences of the United States of America·Frederic A FellouseSachdev S Sidhu
Aug 27, 2004·Glycobiology·Eun Ji JooYeong Shik Kim
Sep 10, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Roberto GennariAlberto Costa
Sep 10, 2005·Nature Biotechnology·Philipp Holliger, Peter J Hudson
Mar 16, 2006·Proceedings of the National Academy of Sciences of the United States of America·Erwin De GenstLode Wyns
Nov 4, 2006·The Journal of Biological Chemistry·Marianela Perez-TorresCarlos L Arteaga
Nov 24, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·G Ramachandra ReddyBrian D Ross
Mar 19, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Antonino MusolinoAndrea Ardizzoni
May 14, 2008·Cancer Genetics and Cytogenetics·Márcia PaivaRui Medeiros
Jan 24, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Frédéric BibeauFlorence Boissière-Michot
May 21, 2009·Experimental and Molecular Pathology·Paula J BatesJohn O Trent
Aug 8, 2009·The Journal of Biological Chemistry·Kerry L InderJohn F Hancock
Apr 13, 2010·Molecular BioSystems·Sara BirtalanSachdev S Sidhu
Nov 27, 2010·Annals of Oncology : Official Journal of the European Society for Medical Oncology·K TamuraY Fujiwara
Jan 25, 2011·Cancer Research·Keren FarinRonit Pinkas-Kramarski
Oct 11, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Greta GarridoLuis Enrique Fernández
Mar 23, 2012·Nature Reviews. Cancer·Andrew M ScottLloyd J Old
May 24, 2012·International Journal of Pharmaceutics·Lígia C Gomes-da-SilvaJoão N Moreira
Apr 27, 2013·Inflammatory Bowel Diseases·Naoyasu UedaTakahiko Horiuchi
Jun 25, 2013·Cancer Research·Mingxia YuZhuoya Li

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Citations

Jan 17, 2021·Pharmaceuticals·Laura Sofia CarvalhoJoão Nuno Moreira
Nov 7, 2020·Chemical Communications : Chem Comm·Junfa YinHailin Wang
Jul 14, 2021·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Jinlong LiuZhimeng Wu

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Methods Mentioned

BETA
flow cytometry
phage display
PCR
enzyme-linked immunosorbent assay

Software Mentioned

RTCA
InCyte

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