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 Abou, Marise R H Van Voss, Peter T. Scardino, Sven Erik Strand, Mary L. AlpaughHoward I. Scher, Hans Lilja, Steven M. Larson, David Ulmert

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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.

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

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Thorek, D. L. J., Watson, P. A., Lee, S. G., Ku, A. T., Bournazos, S., Braun, K., Kim, K., Sjostrom, K., Doran, M. G., Lamminmaki, U., Santos, E., Veach, D., Turkekul, M., Casey, E., Lewis, J. S., Abou, D., Van Voss, M. R. H., Scardino, P. T., Strand, S. E., ... 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, 8(367), [367ra167]. https://doi.org/10.1126/scitranslmed.aaf2335