PMID- 9815926
OWN - NLM
STAT- MEDLINE
DCOM- 19990209
LR  - 20220408
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 1
IP  - 11
DP  - 1995 Nov
TI  - Biological efficacy of a chimeric antibody to the epidermal growth factor 
      receptor in a human tumor xenograft model.
PG  - 1311-8
AB  - The epidermal growth factor receptor (EGFR) is a protein tyrosine kinase 
      expressed on many types of tumor cells, including breast, ovarian, bladder, head 
      and neck, and prostatic carcinoma. There seems to be an association between 
      up-regulation of the EGFR and poor clinical prognosis for a number of human 
      cancers. The 225 antibody is a highly specific murine monoclonal antibody that 
      binds specifically to the human EGFR with an affinity equal to its ligand, 
      competes with the ligand for binding, and blocks activation of the receptor 
      tyrosine kinase. In addition, 225 has been shown to inhibit the growth of human 
      tumor xenografts in athymic nude mice. The 225 antibody has recently been 
      chimerized with human IgG1 in its constant region to increase its clinical 
      utility by decreasing the potential for generation of human antimouse antibodies 
      in recipients. This report compares the biological effects of 225 and its 
      chimeric counterpart (designated C225) against established A431 tumor xenografts 
      in nude mice. The results of these experiments indicated that C225 was more 
      effective than 225 in inhibiting tumor growth in this model. In addition, many of 
      the animals treated with C225 were tumor free at the end of each treatment 
      protocol. It was determined that the dissociation constant of C225 was about 
      5-fold lower than 225. This suggested that the increased capacity of C225 to 
      compete with ligand for binding to the EGFR was responsible for its enhanced in 
      vivo antitumor effect.
FAU - Goldstein, N I
AU  - Goldstein NI
AD  - Departments of Immunology/Monoclonal Antibodies and Protein Chemistry, ImClone 
      Systems, Inc., New York, New York 10014, USA.
FAU - Prewett, M
AU  - Prewett M
FAU - Zuklys, K
AU  - Zuklys K
FAU - Rockwell, P
AU  - Rockwell P
FAU - Mendelsohn, J
AU  - Mendelsohn J
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Immunoglobulin G)
RN  - 0 (Immunoglobulin Variable Region)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Animals
MH  - Drug Screening Assays, Antitumor
MH  - ErbB Receptors/*immunology
MH  - Female
MH  - Humans
MH  - Immunoglobulin G/pharmacology/*therapeutic use
MH  - Immunoglobulin Variable Region/immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Neoplasm Proteins/*immunology
MH  - Recombinant Fusion Proteins/pharmacology/*therapeutic use
MH  - Transplantation, Heterologous
EDAT- 1995/11/01 00:00
MHDA- 1998/11/17 00:01
CRDT- 1995/11/01 00:00
PHST- 1995/11/01 00:00 [pubmed]
PHST- 1998/11/17 00:01 [medline]
PHST- 1995/11/01 00:00 [entrez]
PST - ppublish
SO  - Clin Cancer Res. 1995 Nov;1(11):1311-8.