Internalization of secreted antigen-targeted antibodies by the neonatal Fc receptor for precision imaging of the androgen receptor axis
(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)
- author
- organization
- publishing date
- 2016-11-30
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Science Translational Medicine
- volume
- 8
- issue
- 367
- article number
- 367ra167
- publisher
- American Association for the Advancement of Science (AAAS)
- external identifiers
-
- scopus:85002193746
- pmid:27903863
- 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
- 2024-09-21 06:26:06
@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>}}, 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}}, doi = {{10.1126/scitranslmed.aaf2335}}, volume = {{8}}, year = {{2016}}, }