Advanced

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. LU ; Bournazos, Stylianos; Braun, Katharina; Kim, Kwanghee; Sjostrom, Kjell; Doran, Michael G. and Lamminmaki, Urpo, et al. (2016) In Science Translational Medicine 8(367).
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Science Translational Medicine
volume
8
issue
367
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • scopus:85002193746
  • wos:000389449700002
ISSN
1946-6234
DOI
10.1126/scitranslmed.aaf2335
language
English
LU publication?
yes
id
9d8e09fe-3a87-4bcc-9087-e253cb7c7849
date added to LUP
2016-12-29 10:12:11
date last changed
2017-11-14 09:53:17
@article{9d8e09fe-3a87-4bcc-9087-e253cb7c7849,
  abstract     = {<p>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.</p>},
  articleno    = {367ra167},
  author       = {Thorek, Daniel L J and Watson, Philip A. and Lee, Sang Gyu and Ku, Anson T. and Bournazos, Stylianos and Braun, Katharina and Kim, Kwanghee and Sjostrom, Kjell and Doran, Michael G. and Lamminmaki, Urpo and Santos, Elmer and Veach, Darren and Turkekul, Mesruh and Casey, Emily 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 Lilja, Hans and Larson, Steven M. and Ulmert, David},
  issn         = {1946-6234},
  language     = {eng},
  month        = {11},
  number       = {367},
  publisher    = {American Association for the Advancement of Science (AAAS)},
  series       = {Science Translational Medicine},
  title        = {Internalization of secreted antigen-targeted antibodies by the neonatal Fc receptor for precision imaging of the androgen receptor axis},
  url          = {http://dx.doi.org/10.1126/scitranslmed.aaf2335},
  volume       = {8},
  year         = {2016},
}