@article{996db72036c34eb0b74a00f22706d55e,
title = "Internalization of secreted antigen-targeted antibodies by the neonatal Fc receptor for precision imaging of the androgen receptor axis",
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.",
author = "Thorek, {Daniel L.J.} and Watson, {Philip A.} and Lee, {Sang Gyu} and Ku, {Anson T.} and Stylianos Bournazos and Katharina Braun and Kwanghee Kim and Kjell Sjostrom and Doran, {Michael G.} and Urpo Lamminmaki and Elmer Santos and Darren Veach and Mesruh Turkekul and Emily Casey and Lewis, {Jason S.} and Abou, {Diane S.} and {Van Voss}, {Marise R.H.} and Scardino, {Peter T.} and Strand, {Sven Erik} and Alpaugh, {Mary L.} and Scher, {Howard I.} and Hans Lilja and Larson, {Steven M.} and David Ulmert",
note = "Funding Information: This study was supported in part by the NIH [grants P30 CA008748 (MSKCC Cancer Center Support Grant) and P30 CA006973 (Johns Hopkins University Cancer Center Support Grant)]. The MSKCC Small-Animal Imaging Core Facility is supported in part by the NIH (grants P30 CA008748-48, S10 RR020892-01, and S10 RR028889-01) and the Geoffrey Beene Cancer Research Center. We also acknowledge W. H. Goodwin and A. Goodwin and their Commonwealth Foundation for Cancer Research, the Experimental Therapeutics Center, and the Radiochemistry and Molecular Imaging Probe Core (P50-CA086438); all of MSKCC. D.L.J.T. was supported by the NIH Molecular Imaging Fellowship Program (5R25CA096945-07) and the Steve Wynn Prostate Cancer Foundation Young Investigator Award (PCF-YIA). D.U. was supported in part by the Knut and Alice Wallenberg Foundation, the Bertha Kamprad Foundation, and the David H. Koch PCF-YIA. S.M.L. was supported by the Ludwig Center for Cancer Immunotherapy at the MSKCC and the National Cancer Institute (P50-CA86438); S.-E.S. by the Swedish Cancer Society and the Swedish National Health Foundation (Avtal om L{\"a}karutbildning); H.L. was supported in part by the National Cancer Institute (R33 CA127768-02), the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre program, the Swedish Cancer Society (3455, 14-0722), and the Swedish Research Council (Medicine-20095). P.T.S., H.I.S., and H.L. were supported in part by the MSKCC Specialized Programs of Research Excellence in Prostate Cancer (P50 CA92629), the David H. Koch Fund of the PCF, and the Sidney Kimmel Center for Prostate and Urologic Cancers. D.V. was supported in part by the Hascoe Charitable Foundation Publisher Copyright: {\textcopyright} 2016 The Authors, some rights reserved.",
year = "2016",
month = nov,
day = "30",
doi = "10.1126/scitranslmed.aaf2335",
language = "English",
volume = "8",
journal = "Science translational medicine",
issn = "1946-6234",
number = "367",
}