PMID- 17360479
OWN - NLM
STAT- MEDLINE
DCOM- 20070424
LR  - 20220317
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 104
IP  - 10
DP  - 2007 Mar 6
TI  - A phase I clinical trial with monoclonal antibody ch806 targeting transitional 
      state and mutant epidermal growth factor receptors.
PG  - 4071-6
AB  - An array of cell-surface antigens expressed by human cancers have been identified 
      as targets for antibody-based therapies. The great majority of these antibodies 
      do not have specificity for cancer but recognize antigens expressed on a range of 
      normal cell types (differentiation antigens). Over the past two decades, our 
      group has analyzed thousands of mouse monoclonal antibodies for cancer 
      specificity and identified a battery of antibodies with limited representation on 
      normal human cells. The most tumor-specific of these antibodies is 806, an 
      antibody that detects a unique epitope on the epidermal growth factor receptor 
      (EGFR) that is exposed only on overexpressed, mutant, or ligand-activated forms 
      of the receptor in cancer. In vitro immunohistochemical specificity analysis 
      shows little or no detectable 806 reactivity with normal tissues, even those with 
      high levels of wild-type (wt)EGFR expression. Preclinical studies have 
      demonstrated that 806 specifically targets a subset of EGFR expressed on tumor 
      cells, and has significant anti-tumor effects on human tumor xenografts, 
      primarily through abrogation of signaling pathways. The present clinical study 
      was designed to examine the in vivo specificity of a chimeric form of mAb 806 
      (ch806) in a tumor targeting/biodistribution/pharmacokinetic analysis in patients 
      with diverse tumor types. ch806 showed excellent targeting of tumor sites in all 
      patients, no evidence of normal tissue uptake, and no significant toxicity. These 
      in vitro and in vivo characteristics of ch806 distinguish it from all other 
      antibodies targeting EGFR.
FAU - Scott, Andrew M
AU  - Scott AM
AD  - Ludwig Institute for Cancer Research, 143-165 Studley Road, Heidelberg, 
      Melbourne, Victoria 3084, Australia. andrew.scott@ludwig.edu.au
FAU - Lee, Fook-Thean
AU  - Lee FT
FAU - Tebbutt, Niall
AU  - Tebbutt N
FAU - Herbertson, Rebecca
AU  - Herbertson R
FAU - Gill, Sanjeev S
AU  - Gill SS
FAU - Liu, Zhanqi
AU  - Liu Z
FAU - Skrinos, Effie
AU  - Skrinos E
FAU - Murone, Carmel
AU  - Murone C
FAU - Saunder, Timothy H
AU  - Saunder TH
FAU - Chappell, Bridget
AU  - Chappell B
FAU - Papenfuss, Anthony T
AU  - Papenfuss AT
FAU - Poon, Aurora M T
AU  - Poon AM
FAU - Hopkins, Wendie
AU  - Hopkins W
FAU - Smyth, Fiona E
AU  - Smyth FE
FAU - MacGregor, Duncan
AU  - MacGregor D
FAU - Cher, Lawrence M
AU  - Cher LM
FAU - Jungbluth, Achim A
AU  - Jungbluth AA
FAU - Ritter, Gerd
AU  - Ritter G
FAU - Brechbiel, Martin W
AU  - Brechbiel MW
FAU - Murphy, Roger
AU  - Murphy R
FAU - Burgess, Antony W
AU  - Burgess AW
FAU - Hoffman, Eric W
AU  - Hoffman EW
FAU - Johns, Terrance G
AU  - Johns TG
FAU - Old, Lloyd J
AU  - Old LJ
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070228
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Indium Radioisotopes)
RN  - 0 (monoclonal antibody 806)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
EIN - Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15965. Ritter, Gerd [added]
MH  - Aged
MH  - Antibodies, Monoclonal/chemistry/*pharmacokinetics/*therapeutic use
MH  - Antineoplastic Agents/therapeutic use
MH  - Cell Line, Tumor
MH  - Cell Membrane/metabolism
MH  - ErbB Receptors/*metabolism
MH  - Female
MH  - Humans
MH  - Immunotherapy/instrumentation/*methods
MH  - Indium Radioisotopes/pharmacology
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Transplantation
MH  - Neoplasms/*drug therapy/*immunology
MH  - Signal Transduction
PMC - PMC1805701
COIS- Conflict of interest statement: A.M.S., A.A.J., A.W.B., T.G.J., and L.J.O. are 
      coinventors of a patent for monoclonal antibody 806. A.M.S. and F.E.S. are 
      consultants to Life Sciences Pharmaceuticals, which has the license for ch806. 
      L.J.O. is a noncompensated board member of Life Sciences Pharmaceuticals.
EDAT- 2007/03/16 09:00
MHDA- 2007/04/25 09:00
PMCR- 2007/03/06
CRDT- 2007/03/16 09:00
PHST- 2007/03/16 09:00 [pubmed]
PHST- 2007/04/25 09:00 [medline]
PHST- 2007/03/16 09:00 [entrez]
PHST- 2007/03/06 00:00 [pmc-release]
AID - 0611693104 [pii]
AID - 5378 [pii]
AID - 10.1073/pnas.0611693104 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4071-6. doi: 
      10.1073/pnas.0611693104. Epub 2007 Feb 28.