Potent antitumor activity of an auristatin-conjugated, fully human monoclonal antibody to prostate-specific membrane antigen

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Dangshe MaWilliam C Olson

Abstract

Prostate-specific membrane antigen (PSMA) is the prototypic cell-surface marker of prostate cancer and provides an attractive target for monoclonal antibody (mAb) targeted therapies. In this study, a novel antibody-drug conjugate (ADC) was generated by linking a fully human PSMA mAb to monomethylauristatin E (MMAE), a potent inhibitor of tubulin polymerization. The PSMA ADC was evaluated for antitumor activity in vitro and in a mouse xenograft model of androgen-independent human prostate cancer. The PSMA ADC eliminated PSMA-expressing cells with picomolar potency and >700-fold selectivity in culture. When used to treat mice with established human C4-2 tumors, the PSMA ADC significantly improved median survival 9-fold relative to vehicle or isotype-matched ADC (P = 0.0018) without toxicity. Treatment effects were also manifest as significant (P = 0.0068) reduction in serum levels of prostate-specific antigen (PSA). Importantly, 40% of treated animals had no detectable tumor or measurable PSA at day 500 and could be considered cured. The findings support development of PSMA antibody-auristatin conjugates for therapy of prostate cancer.

References

Aug 1, 1997·Cancer Biotherapy & Radiopharmaceuticals·R O Dillman
Mar 17, 2001·Nature Reviews. Molecular Cell Biology·Y Yarden, M X Sliwkowski
Jun 5, 2002·Nature Reviews. Cancer·Samuel R Denmeade, John T Isaacs
Jul 13, 2002·Expert Review of Anticancer Therapy·Francis J Dumont
Oct 18, 2002·Expert Review of Anticancer Therapy·Antonio J Grillo-López
May 9, 2003·The Urologic Clinics of North America·Eric A Klein, Patrick A Kupelian
Jun 5, 2003·Nature Biotechnology·Svetlana O DoroninaPeter D Senter
Oct 7, 2003·Molecular Biology of the Cell·Sigrid A RajasekaranAyyappan K Rajasekaran
Oct 30, 2003·Proceedings of the National Academy of Sciences of the United States of America·Norbert SchülkeWilliam C Olson
Feb 12, 2004·Cancer Research·Weiguang MaoPaul Polakis
Jun 4, 2004·The New England Journal of Medicine·Herbert HurwitzFairooz Kabbinavar
Jul 22, 2004·American Journal of Therapeutics·James Gulley, William L Dahut
Jul 23, 2004·The New England Journal of Medicine·David CunninghamEric Van Cutsem
Oct 8, 2004·The New England Journal of Medicine·Daniel P PetrylakE David Crawford
Oct 27, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kevin J HamblettJoseph A Francisco
Dec 9, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Che-Leung LawAlan F Wahl
Jan 22, 2005·CA: a Cancer Journal for Clinicians·Ahmedin JemalMichael J Thun
Feb 4, 2005·The New England Journal of Medicine·Mark S KaminskiRichard L Wahl
Apr 20, 2005·Proceedings of the National Academy of Sciences of the United States of America·Mindy I DavisPamela J Bjorkman

❮ Previous
Next ❯

Citations

Jul 31, 2007·Cancer Immunology, Immunotherapy : CII·Valeska HofmeisterJürgen C Becker
Jul 11, 2012·Pharmaceutical Research·Gary D Stack, John J Walsh
Jun 10, 2008·The Cancer Journal·Paul J Carter, Peter D Senter
Aug 4, 2011·Advances in Urology·Naveed H AkhtarScott T Tagawa
May 1, 2009·Immunotherapy·Patrick BühlerUrsula Elsässer-Beile
Mar 15, 2011·Immunotherapy·Francois Fay, Christopher J Scott
Mar 1, 2011·Therapeutic Delivery·Victor S Goldmacher, Yelena V Kovtun
Jul 22, 2008·Nature Biotechnology·Jagath R JunutulaWilliam Mallet
May 24, 2011·Expert Opinion on Investigational Drugs·Puja SapraHans-Peter Gerber
Dec 22, 2007·Expert Opinion on Drug Delivery·Michael J BrumlikTyler J Curiel
Mar 24, 2015·Expert Opinion on Drug Discovery·Mahendra P DeonarainJared Marklew
Jul 22, 2006·Expert Opinion on Biological Therapy·D K Wilkins, A Mayer
Jul 11, 2008·Expert Opinion on Biological Therapy·Mahendra P Deonarain
Jun 17, 2011·Expert Opinion on Biological Therapy·Guru SonpavdePhilip W Kantoff
Jun 29, 2013·Seminars in Oncology·Alexandra SnyderSusan F Slovin
Apr 19, 2011·Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine·Noeen MalikBoris Zlatopolskiy
May 6, 2009·Current Opinion in Chemical Biology·Peter D Senter
Aug 15, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Alejandro M S Mayer, Kirk R Gustafson
Aug 10, 2007·Journal of Cellular Biochemistry·Xinning WangWarren D W Heston
Dec 3, 2010·The Journal of Pathology·Michael Allen, J Louise Jones
Sep 13, 2014·Angewandte Chemie·Sumith A KularatnePeter G Schultz
Jan 15, 2015·Pharmaceutical Research·Marc DamelinPuja Sapra
Oct 19, 2013·MAbs·Christopher R Behrens, Bin Liu
Feb 1, 2014·European Journal of Medicinal Chemistry·Isabelle Tranoy-OpalinskiSébastien Papot
Jun 1, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Ashutosh BarveKun Cheng
Jul 28, 2018·PloS One·David A EavaroneBo R Rueda
Sep 25, 2018·Journal of Cellular Physiology·Meghdad Abdollahpour-AlitappehMohsen Abolhassani
May 18, 2018·Medicinal Research Reviews·Till WüstemannWalter Mier

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.