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Internalization of secreted antigen-targeted antibodies by the neonatal Fc receptor for precision imaging of the androgen receptor axis

Author:
  • Daniel L J Thorek
  • Philip A. Watson
  • Sang Gyu Lee
  • Anson T. Ku
  • Stylianos Bournazos
  • Katharina Braun
  • Kwanghee Kim
  • Kjell Sjostrom
  • Michael G. Doran
  • Urpo Lamminmaki
  • Elmer Santos
  • Darren Veach
  • Mesruh Turkekul
  • Emily Casey
  • Jason S. Lewis
  • Diane S. Abou
  • Marise R H Van Voss
  • Peter T. Scardino
  • Sven Erik Strand
  • Mary L. Alpaugh
  • Howard I. Scher
  • Hans Lilja
  • Steven M. Larson
  • David Ulmert
Publishing year: 2016-11-30
Language: English
Publication/Series: Science Translational Medicine
Volume: 8
Issue: 367
Document type: Journal article
Publisher: American Association for the Advancement of Science (AAAS)

Abstract english

Targeting the androgen receptor (AR) pathway prolongs survival in patients with prostate cancer, but resistance rapidly develops. Understanding this resistance is confounded by a lack of noninvasive means to assess AR activity in vivo. We report intracellular accumulation of a secreted antigen-targeted antibody (SATA) that can be used to characterize disease, guide therapy, and monitor response. AR-regulated human kallikrein-related peptidase 2 (free hK2) is a prostate tissue-specific antigen produced in prostate cancer and androgen-stimulated breast cancer cells. Fluorescent and radio conjugates of 11B6, an antibody targeting free hK2, are internalized and noninvasively report AR pathway activity in metastatic and genetically engineered models of cancer development and treatment. Uptake is mediated by a mechanism involving the neonatal Fc receptor. Humanized 11B6, which has undergone toxicological tests in nonhuman primates, has the potential to improve patient management in these cancers. Furthermore, cellspecific SATA uptake may have a broader use for molecularly guided diagnosis and therapy in other cancers.

Keywords

  • Urology and Nephrology
  • Cancer and Oncology

Other

Published
  • Clinical Chemistry, Malmö
  • Urological research, Malmö
  • ISSN: 1946-6234
Sven-Erik Strand
E-mail: sven-erik.strand [at] med.lu.se

Project manager

Systemic Radiation Therapy Group

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Professor emeritus

Medical Radiation Physics, Lund

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