Journal
SCIENCE TRANSLATIONAL MEDICINE
Volume 8, Issue 367, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aaf2335
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Categories
Funding
- NIH [P30 CA008748, P30 CA006973, P30 CA008748-48, S10 RR020892-01, S10 RR028889-01, 5R25CA096945-07]
- Geoffrey Beene Cancer Research Center
- Steve Wynn Prostate Cancer Foundation Young Investigator Award (PCF-YIA)
- Knut and Alice Wallenberg Foundation
- Bertha Kamprad Foundation
- Ludwig Center for Cancer Immunotherapy at the MSKCC
- National Cancer Institute [P50-CA86438, R33 CA127768-02]
- Swedish Cancer Society [3455, 14-0722]
- Swedish National Health Foundation (Avtal om Lakarutbildning)
- National Institute for Health Research (NIHR) Oxford Biomedical Research Centre program
- Swedish Research Council [Medicine-20095]
- MSKCC Specialized Programs of Research Excellence in Prostate Cancer [P50 CA92629]
- David H. Koch Fund of the PCF
- Sidney Kimmel Center for Prostate and Urologic Cancers
- Hascoe Charitable Foundation
- David H. Koch PCF-YIA
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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, cell-specific SATA uptake may have a broader use for molecularly guided diagnosis and therapy in other cancers.
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