PMID- 7606735
OWN - NLM
STAT- MEDLINE
DCOM- 19950817
LR  - 20210103
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 55
IP  - 14
DP  - 1995 Jul 15
TI  - Monoclonal antibodies against EGFRvIII are tumor specific and react with breast 
      and lung carcinomas and malignant gliomas.
PG  - 3140-8
AB  - Despite molecular biological advances in understanding human cancers, translation 
      into therapy has been less forthcoming; targeting neoplastic cells still requires 
      that tumor-specific markers, preferably those on the cell surface, be identified. 
      The epidermal growth factor receptor (EGFR) exists in a deletion-mutant form, 
      EGFRvIII, which has been identified by genetic and immunological means in a 
      subset of gliomas and non-small cell lung carcinomas. Specific polyvalent 
      antisera to the extracellular portion of the variant were readily induced, but 
      immunization using a synthetic linear peptide representing the unique EGFRvIII 
      primary sequence has been unsuccessful in mice or macaques. We report here five 
      specific monoclonal antibodies (mAbs) developed through long-term immunization 
      protocols using the EGFRvIII-specific synthetic peptide and the intact variant in 
      different formats that maintained secondary and tertiary conformation. These mAbs 
      identify the EGFRvIII on the cell surface with relatively high affinity (KA 
      range, 0.13 to 2.5 x 10(9) M-1) by live cell Scatchard analysis. These mAbs are 
      specific for EGFRvIII as determined by RIA, ELISA, Western blot, analytical flow 
      cytometry, autophosphorylation, and immunohistochemistry. Isolating specific mAbs 
      enabled us to analyze normal and neoplastic human tissue and establish that 
      EGFRvIII is truly tumor specific for subsets of breast carcinomas and for 
      previously reported non-small cell lung carcinomas and gliomas. Also, this 
      receptor is not expressed by any normal human tissues thus far examined, 
      including elements of the peripheral, central nervous, and lymphoid systems. With 
      mAbs, we identified a higher incidence of EGFRvIII positivity in gliomas than 
      previously described and identified an EGFRvIII-positive subset of breast tumors; 
      also, we observed that the EGFRvIII epitope is not expressed in normal tissues, 
      and we demonstrated the localizing and therapeutic potential of the mAbs for 
      tumors expressing this epitope. Our observations strongly warrant development of 
      this mAb-antigen system as therapy for breast, lung, and central nervous system 
      tumors.
FAU - Wikstrand, C J
AU  - Wikstrand CJ
AD  - Department of Pathology, Duke University Medical Center, Durham, North Carolina 
      27710, USA.
FAU - Hale, L P
AU  - Hale LP
FAU - Batra, S K
AU  - Batra SK
FAU - Hill, M L
AU  - Hill ML
FAU - Humphrey, P A
AU  - Humphrey PA
FAU - Kurpad, S N
AU  - Kurpad SN
FAU - McLendon, R E
AU  - McLendon RE
FAU - Moscatello, D
AU  - Moscatello D
FAU - Pegram, C N
AU  - Pegram CN
FAU - Reist, C J
AU  - Reist CJ
AU  - et al.
LA  - eng
GR  - CA 11898/CA/NCI NIH HHS/United States
GR  - CA 32672/CA/NCI NIH HHS/United States
GR  - CA 56115/CA/NCI NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
GS  - EGFR
GS  - c-erbB-1
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antibodies, Monoclonal/*immunology/isolation & purification/metabolism
MH  - Antibody Specificity
MH  - Base Sequence
MH  - Breast Neoplasms/immunology/metabolism/*ultrastructure
MH  - ErbB Receptors/classification/genetics/*immunology
MH  - Female
MH  - Glioma/immunology/metabolism/*ultrastructure
MH  - Humans
MH  - Immunohistochemistry
MH  - Kinetics
MH  - Lung Neoplasms/immunology/metabolism/*ultrastructure
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Molecular Sequence Data
MH  - Neoplasm Transplantation
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/analysis/genetics
MH  - Transcription, Genetic
MH  - Transplantation, Heterologous
MH  - Tumor Cells, Cultured
EDAT- 1995/07/15 00:00
MHDA- 1995/07/15 00:01
CRDT- 1995/07/15 00:00
PHST- 1995/07/15 00:00 [pubmed]
PHST- 1995/07/15 00:01 [medline]
PHST- 1995/07/15 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1995 Jul 15;55(14):3140-8.