PMID- 26073904
OWN - NLM
STAT- MEDLINE
DCOM- 20160613
LR  - 20201209
IS  - 1942-0870 (Electronic)
IS  - 1942-0862 (Print)
IS  - 1942-0862 (Linking)
VI  - 7
IP  - 5
DP  - 2015
TI  - A bi-functional antibody-receptor domain fusion protein simultaneously targeting 
      IGF-IR and VEGF for degradation.
PG  - 931-45
LID - 10.1080/19420862.2015.1055442 [doi]
AB  - Bi-specific antibodies (BsAbs), which can simultaneously block 2 tumor targets, 
      have emerged as promising therapeutic alternatives to combinations of individual 
      monoclonal antibodies. Here, we describe the engineering and development of a 
      novel, human bi-functional antibody-receptor domain fusion molecule with ligand 
      capture (bi-AbCap) through the fusion of the domain 2 of human vascular 
      endothelial growth factor receptor 1 (VEGFR1) to an antibody directed against 
      insulin-like growth factor - type I receptor (IGF-IR). The bi-AbCap possesses 
      excellent stability and developability, and is the result of minimal engineering. 
      Beyond potent neutralizing activities against IGF-IR and VEGF, the bi-AbCap is 
      capable of cross-linking VEGF to IGF-IR, leading to co-internalization and 
      degradation of both targets by tumor cells. In multiple mouse xenograft tumor 
      models, the bi-AbCap improves anti-tumor activity over individual monotherapies. 
      More importantly, it exhibits superior inhibition of tumor growth, compared with 
      the combination of anti-IGF-IR and anti-VEGF therapies, via powerful blockade of 
      both direct tumor cell growth and tumor angiogenesis. The unique 
      "capture-for-degradation" mechanism of the bi-AbCap is informative for the design 
      of next-generation bi-functional anti-cancer therapies directed against 
      independent signaling pathways. The bi-AbCap design represents an alternative 
      approach to the creation of dual-targeting antibody fusion molecules by taking 
      advantage of natural receptor-ligand interactions.
FAU - Shen, Yang
AU  - Shen Y
AD  - a Antibody Technology; Eli Lilly and Company ; New York , NY USA.
FAU - Zeng, Lin
AU  - Zeng L
FAU - Novosyadlyy, Ruslan
AU  - Novosyadlyy R
FAU - Forest, Amelie
AU  - Forest A
FAU - Zhu, Aiping
AU  - Zhu A
FAU - Korytko, Andrew
AU  - Korytko A
FAU - Zhang, Haifan
AU  - Zhang H
FAU - Eastman, Scott W
AU  - Eastman SW
FAU - Topper, Michael
AU  - Topper M
FAU - Hindi, Sagit
AU  - Hindi S
FAU - Covino, Nicole
AU  - Covino N
FAU - Persaud, Kris
AU  - Persaud K
FAU - Kang, Yun
AU  - Kang Y
FAU - Burtrum, Douglas
AU  - Burtrum D
FAU - Surguladze, David
AU  - Surguladze D
FAU - Prewett, Marie
AU  - Prewett M
FAU - Chintharlapalli, Sudhakar
AU  - Chintharlapalli S
FAU - Wroblewski, Victor J
AU  - Wroblewski VJ
FAU - Shen, Juqun
AU  - Shen J
FAU - Balderes, Paul
AU  - Balderes P
FAU - Zhu, Zhenping
AU  - Zhu Z
FAU - Snavely, Marshall
AU  - Snavely M
FAU - Ludwig, Dale L
AU  - Ludwig DL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - MAbs
JT  - mAbs
JID - 101479829
RN  - 0 (Antibodies, Bispecific)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (IGF1R protein, human)
RN  - 0 (Receptors, Somatomedin)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
SB  - IM
MH  - Animals
MH  - Antibodies, Bispecific/*pharmacology
MH  - Antibodies, Monoclonal/pharmacology
MH  - Antibodies, Neutralizing/*pharmacology
MH  - Antibody Affinity
MH  - Chromatography, High Pressure Liquid
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Humans
MH  - Immunoblotting
MH  - Immunoprecipitation
MH  - Mice
MH  - Mice, Nude
MH  - Microscopy, Confocal
MH  - Neoplasms, Experimental/drug therapy
MH  - Protein Stability
MH  - Receptor, IGF Type 1
MH  - Receptors, Somatomedin/*antagonists & inhibitors
MH  - Recombinant Fusion Proteins/*pharmacology
MH  - Surface Plasmon Resonance
MH  - Vascular Endothelial Growth Factor A/*antagonists & inhibitors
MH  - Xenograft Model Antitumor Assays
PMC - PMC4623440
OTO - NOTNLM
OT  - IGF-IR
OT  - VEGF
OT  - VEGFR1
OT  - VEGFR2
OT  - angiogenesis
OT  - antibody fusion
OT  - bi-functional antibody
OT  - bispecific antibody
OT  - degradation
OT  - internalization
EDAT- 2015/06/16 06:00
MHDA- 2016/06/14 06:00
PMCR- 2016/02/03
CRDT- 2015/06/16 06:00
PHST- 2015/06/16 06:00 [entrez]
PHST- 2015/06/16 06:00 [pubmed]
PHST- 2016/06/14 06:00 [medline]
PHST- 2016/02/03 00:00 [pmc-release]
AID - 1055442 [pii]
AID - 10.1080/19420862.2015.1055442 [doi]
PST - ppublish
SO  - MAbs. 2015;7(5):931-45. doi: 10.1080/19420862.2015.1055442.