Internalization of secreted antigen-targeted antibodies by the neonatal Fc receptor for precision imaging of the androgen receptor axis

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • Daniel L J Thorek
  • Philip A. Watson
  • Sang Gyu Lee
  • 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 S. Abou
  • Marise R H Van Voss
  • Peter T. Scardino
  • Mary L. Alpaugh
  • Howard I. Scher
  • Steven M. Larson
Enheter & grupper
Externa organisationer
  • Memorial Sloan-Kettering Cancer Center
  • Rockefeller University
  • Ruhr-University Bochum
  • Innovagen AB
  • University of Turku
  • Weill Cornell Medical College
  • Johns Hopkins University School of Medicine
  • University Medical Center Utrecht
  • Rowan University
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Urologi och njurmedicin
  • Cancer och onkologi
Originalspråkengelska
Artikelnummer367ra167
TidskriftScience Translational Medicine
Volym8
Utgivningsnummer367
StatusPublished - 2016 nov 30
PublikationskategoriForskning
Peer review utfördJa