PMID- 28377489
OWN - NLM
STAT- MEDLINE
DCOM- 20180328
LR  - 20200930
IS  - 1538-8514 (Electronic)
IS  - 1535-7163 (Linking)
VI  - 16
IP  - 7
DP  - 2017 Jul
TI  - Preclinical Activity of the Novel Anti-Prolactin Receptor (PRLR) Antibody-Drug 
      Conjugate REGN2878-DM1 in PRLR-Positive Breast Cancers.
PG  - 1299-1311
LID - 10.1158/1535-7163.MCT-16-0839 [doi]
AB  - The Prolactin Receptor (PRLR) is a type 1 cytokine receptor that is expressed in 
      a subset of breast cancers and may contribute to its pathogenesis. It is 
      relatively overexpressed in approximately 25% of human breast tumors while 
      expressed at low levels in some normal human tissues including the mammary gland. 
      We developed an anti-PRLR antibody-drug conjugate (ADC), to target PRLR-positive 
      breast cancer. REGN2878-DM1 is comprised of a fully human high-affinity 
      function-blocking anti-PRLR IgG1 antibody (REGN2878) conjugated via a 
      noncleavable SMCC linker to the cytotoxic maytansine derivative DM1. Both 
      unconjugated REGN2878 and conjugated REGN2878-DM1 block PRL-mediated activation 
      in vitro and are rapidly internalized into lysosomes. REGN2878-DM1 induces potent 
      cell-cycle arrest and cytotoxicity in PRLR-expressing tumor cell lines. In vivo, 
      REGN2878-DM1 demonstrated significant antigen-specific antitumor activity against 
      breast cancer xenograft models. In addition, REGN2878-DM1 showed additive 
      activity when combined with the antiestrogen agent fulvestrant. These results 
      illustrate promising antitumor activity against PRLR-positive breast cancer 
      xenografts and support the evaluation of anti-PRLR ADCs as potential therapeutic 
      agents in breast cancer. Mol Cancer Ther; 16(7); 1299-311. (c)2017 AACR.
CI  - (c)2017 American Association for Cancer Research.
FAU - Kelly, Marcus P
AU  - Kelly MP
AD  - Regeneron Pharmaceuticals, Inc., Tarrytown, New York. marcus.kelly@regeneron.com.
FAU - Hickey, Carlos
AU  - Hickey C
AD  - Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
FAU - Makonnen, Sosina
AU  - Makonnen S
AD  - Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
FAU - Coetzee, Sandra
AU  - Coetzee S
AD  - Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
FAU - Jalal, Sumreen
AU  - Jalal S
AD  - Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
FAU - Wang, Yu
AU  - Wang Y
AD  - Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
FAU - Delfino, Frank
AU  - Delfino F
AD  - Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
FAU - Shan, Jing
AU  - Shan J
AD  - Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
FAU - Potocky, Terra B
AU  - Potocky TB
AD  - Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
FAU - Chatterjee, Ishita
AU  - Chatterjee I
AD  - Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
FAU - Andreev, Julian
AU  - Andreev J
AD  - Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
FAU - Kunz, Arthur
AU  - Kunz A
AD  - Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
FAU - D'Souza, Christopher
AU  - D'Souza C
AD  - Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
FAU - Giurleo, Jason T
AU  - Giurleo JT
AD  - Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
FAU - Nittoli, Thomas
AU  - Nittoli T
AD  - Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
FAU - Trail, Pamela A
AU  - Trail PA
AD  - Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
FAU - Thurston, Gavin
AU  - Thurston G
AD  - Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
FAU - Kirshner, Jessica R
AU  - Kirshner JR
AD  - Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170404
PL  - United States
TA  - Mol Cancer Ther
JT  - Molecular cancer therapeutics
JID - 101132535
RN  - 0 (Antibodies, Anti-Idiotypic)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Immunoconjugates)
RN  - 0 (Receptors, Prolactin)
SB  - IM
MH  - Animals
MH  - Antibodies, Anti-Idiotypic/administration & dosage/immunology
MH  - Antibodies, Monoclonal, Humanized/*administration & dosage/immunology
MH  - Breast Neoplasms/*drug therapy/genetics/immunology/pathology
MH  - Cell Proliferation/drug effects
MH  - Female
MH  - Humans
MH  - Immunoconjugates/*administration & dosage/immunology
MH  - Mice
MH  - Receptors, Prolactin/genetics/*immunology
MH  - Xenograft Model Antitumor Assays
EDAT- 2017/04/06 06:00
MHDA- 2018/03/29 06:00
CRDT- 2017/04/06 06:00
PHST- 2016/12/06 00:00 [received]
PHST- 2017/03/21 00:00 [revised]
PHST- 2017/03/29 00:00 [accepted]
PHST- 2017/04/06 06:00 [pubmed]
PHST- 2018/03/29 06:00 [medline]
PHST- 2017/04/06 06:00 [entrez]
AID - 1535-7163.MCT-16-0839 [pii]
AID - 10.1158/1535-7163.MCT-16-0839 [doi]
PST - ppublish
SO  - Mol Cancer Ther. 2017 Jul;16(7):1299-1311. doi: 10.1158/1535-7163.MCT-16-0839. 
      Epub 2017 Apr 4.