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

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 & 4 others Howard I. Scher, Hans Lilja, Steven M. Larson, David Ulmert

Research output: Research - peer-reviewArticle

Abstract

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.

LanguageEnglish (US)
Article number367ra167
JournalScience Translational Medicine
Volume8
Issue number367
DOIs
StatePublished - Nov 30 2016

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Androgen Receptors
Antigens
Antibodies
neonatal Fc receptors
Neoplasms
Therapeutics
Prostatic Neoplasms
Prostate-Specific Antigen
Radio
Toxicology
Primates
Androgens
Breast Neoplasms
Survival
human KLK2 protein

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Internalization of secreted antigen-targeted antibodies by the neonatal Fc receptor for precision imaging of the androgen receptor axis. / Thorek, Daniel L J; Watson, Philip A.; Lee, Sang Gyu; Ku, Anson T.; Bournazos, Stylianos; Braun, Katharina; Kim, Kwanghee; Sjostrom, Kjell; Doran, Michael G.; Lamminmaki, Urpo; Santos, Elmer; Veach, Darren; Turkekul, Mesruh; Casey, Emily; Lewis, Jason S.; Abou, Diane S.; Van Voss, Marise R H; Scardino, Peter T.; Strand, Sven Erik; Alpaugh, Mary L.; Scher, Howard I.; Lilja, Hans; Larson, Steven M.; Ulmert, David.

In: Science Translational Medicine, Vol. 8, No. 367, 367ra167, 30.11.2016.

Research output: Research - peer-reviewArticle

Thorek, DLJ, Watson, PA, Lee, SG, Ku, AT, Bournazos, S, Braun, K, Kim, K, Sjostrom, K, Doran, MG, Lamminmaki, U, Santos, E, Veach, D, Turkekul, M, Casey, E, Lewis, JS, Abou, DS, Van Voss, MRH, Scardino, PT, Strand, SE, Alpaugh, ML, Scher, HI, Lilja, H, Larson, SM & Ulmert, D 2016, 'Internalization of secreted antigen-targeted antibodies by the neonatal Fc receptor for precision imaging of the androgen receptor axis' Science Translational Medicine, vol 8, no. 367, 367ra167. DOI: 10.1126/scitranslmed.aaf2335
Thorek, Daniel L J ; Watson, Philip A. ; Lee, Sang Gyu ; Ku, Anson T. ; Bournazos, Stylianos ; Braun, Katharina ; Kim, Kwanghee ; Sjostrom, Kjell ; Doran, Michael G. ; Lamminmaki, Urpo ; Santos, Elmer ; Veach, Darren ; Turkekul, Mesruh ; Casey, Emily ; Lewis, Jason S. ; Abou, Diane S. ; Van Voss, Marise R H ; Scardino, Peter T. ; Strand, Sven Erik ; Alpaugh, Mary L. ; Scher, Howard I. ; Lilja, Hans ; Larson, Steven M. ; Ulmert, David. / Internalization of secreted antigen-targeted antibodies by the neonatal Fc receptor for precision imaging of the androgen receptor axis. In: Science Translational Medicine. 2016 ; Vol. 8, No. 367.
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