Characterization of ABBV-221, a Tumor-Selective EGFR-Targeting Antibody Drug Conjugate

Molecular Cancer Therapeutics
Andrew C PhillipsEdward B Reilly

Abstract

Depatuxizumab mafodotin (depatux-m, ABT-414) is a tumor-selective antibody drug conjugate (ADC) comprised of the anti-EGFR antibody ABT-806 and the monomethyl auristatin F (MMAF) warhead. Depatux-m has demonstrated promising clinical activity in glioblastoma multiforme (GBM) patients and is currently being evaluated in clinical trials in first-line and recurrent GBM disease settings. Depatux-m responses have been restricted to patients with amplified EGFR, highlighting the need for therapies with activity against tumors with nonamplified EGFR overexpression. In addition, depatux-m dosing has been limited by corneal side effects common to MMAF conjugates. We hypothesized that a monomethyl auristatin E (MMAE) ADC utilizing an EGFR-targeting antibody with increased affinity may have broader utility against tumors with more modest EGFR overexpression while mitigating the risk of corneal side effects. We describe here preclinical characterization of ABBV-221, an EGFR-targeting ADC comprised of an affinity-matured ABT-806 conjugated to MMAE. ABBV-221 binds to a similar EGFR epitope as depatux-m and retains tumor selectivity with increased binding to EGFR-positive tumor cells and greater in vitro potency. ABBV-221 displays increased t...Continue Reading

References

Jun 5, 2003·Nature Biotechnology·Svetlana O DoroninaPeter D Senter
Jun 27, 2003·Advances in Anatomic Pathology·Charles HillDaniel J Brat
Oct 7, 2003·Molecular Cell·Antony W BurgessShigeyuki Yokoyama
Jul 21, 2004·Journal of Immunological Methods·Michael J Feldhaus, Robert W Siegel
Sep 16, 2005·Expert Review of Neurotherapeutics·Deborah T Blumenthal, Susan F Schulman
Mar 15, 2006·Archives of Neurology·John W Henson
Aug 8, 2006·Seminars in Oncology·John Mendelsohn, Jose Baselga
Sep 6, 2008·Nature·UNKNOWN Cancer Genome Atlas Research Network
Mar 18, 2009·Proceedings of the National Academy of Sciences of the United States of America·Thomas P J GarrettTerrance G Johns
May 20, 2009·Targeted Oncology·Tianhong Li, Roman Perez-Soler
Sep 9, 2010·Neoplasia : an International Journal for Oncology Research·Kimmo J HatanpaaAmyn A Habib
Sep 11, 2012·Nature·UNKNOWN Cancer Genome Atlas Research Network
Nov 10, 2013·Nature Medicine·Curtis R Chong, Pasi A Jänne
Mar 26, 2014·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Jean-Yves DouillardFrances A Shepherd
Sep 1, 2014·Seminars in Oncology·Derek R Johnson, Evanthia Galanis
Jan 30, 2015·Nature·UNKNOWN Cancer Genome Atlas Network
Mar 4, 2015·Molecular Cancer Therapeutics·Edward B ReillyAndrew M Scott
May 16, 2015·The American Journal of Pathology·Ines CrespoMaria Dolores Tabernero
Jun 11, 2015·Methods in Molecular Biology·Gerald M Cherf, Jennifer R Cochran
Nov 6, 2015·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Joshua Seth EatonChristopher J Murphy
Feb 6, 2016·Molecular Cancer Therapeutics·Andrew C PhillipsEdward B Reilly

❮ Previous
Next ❯

Citations

Jun 5, 2019·Marine Drugs·David J Newman
Jan 13, 2019·Targeted Oncology·Zhuanglin LiChangjiang Huang
Apr 28, 2020·JNCI Cancer Spectrum·Paul GougisChristophe Le Tourneau
May 24, 2020·Current Neurology and Neuroscience Reports·Elisa K LiuSylvia C Kurz
Aug 22, 2018·Molecular Cancer Therapeutics·Jan-Willem TheunissenThi-Sau Migone
Aug 28, 2020·Molecular Cancer Therapeutics·Mark G AndersonEdward B Reilly
Dec 10, 2020·Marine Drugs·Marilia BarrecaFrancesco Bertoni
Jan 17, 2021·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Puey Ling ChiaThomas John
Mar 24, 2020·Chemical Reviews·Weijun WeiWeibo Cai
Nov 15, 2020·International Journal of Pharmaceutics·Elias da Silva SantosJosimar O Eloy

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Stem Cells in Glioblastoma

Glioblastoma is the most common and aggressive type of brain tumor. It contains a population of tumor initiating stem cell-like cells known as cancer stem cells. Investigations are ongoing into these cancer stem cells found in these solid tumors which are highly resistance to treatment. Here is the latest research on cancer stem cells in glioblastoma.