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Monoclonal antibodies against EGFRvIII are tumor specific and react with breast and lung carcinomas and malignant gliomas.

Publication ,  Journal Article
Wikstrand, CJ; Hale, LP; Batra, SK; Hill, ML; Humphrey, PA; Kurpad, SN; McLendon, RE; Moscatello, D; Pegram, CN; Reist, CJ
Published in: Cancer Res
July 15, 1995

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.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

July 15, 1995

Volume

55

Issue

14

Start / End Page

3140 / 3148

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Transcription, Genetic
  • RNA, Messenger
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Molecular Sequence Data
  • Mice, Inbred BALB C
  • Mice
 

Citation

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Wikstrand, C. J., Hale, L. P., Batra, S. K., Hill, M. L., Humphrey, P. A., Kurpad, S. N., … Reist, C. J. (1995). Monoclonal antibodies against EGFRvIII are tumor specific and react with breast and lung carcinomas and malignant gliomas. Cancer Res, 55(14), 3140–3148.
Wikstrand, C. J., L. P. Hale, S. K. Batra, M. L. Hill, P. A. Humphrey, S. N. Kurpad, R. E. McLendon, D. Moscatello, C. N. Pegram, and C. J. Reist. “Monoclonal antibodies against EGFRvIII are tumor specific and react with breast and lung carcinomas and malignant gliomas.Cancer Res 55, no. 14 (July 15, 1995): 3140–48.
Wikstrand CJ, Hale LP, Batra SK, Hill ML, Humphrey PA, Kurpad SN, et al. Monoclonal antibodies against EGFRvIII are tumor specific and react with breast and lung carcinomas and malignant gliomas. Cancer Res. 1995 Jul 15;55(14):3140–8.
Wikstrand, C. J., et al. “Monoclonal antibodies against EGFRvIII are tumor specific and react with breast and lung carcinomas and malignant gliomas.Cancer Res, vol. 55, no. 14, July 1995, pp. 3140–48.
Wikstrand CJ, Hale LP, Batra SK, Hill ML, Humphrey PA, Kurpad SN, McLendon RE, Moscatello D, Pegram CN, Reist CJ. Monoclonal antibodies against EGFRvIII are tumor specific and react with breast and lung carcinomas and malignant gliomas. Cancer Res. 1995 Jul 15;55(14):3140–3148.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

July 15, 1995

Volume

55

Issue

14

Start / End Page

3140 / 3148

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Transcription, Genetic
  • RNA, Messenger
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Molecular Sequence Data
  • Mice, Inbred BALB C
  • Mice