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Immune responses of breast cancer patients to mutated epidermal growth factor receptor (EGF-RvIII, Delta EGF-R, and de2-7 EGF-R).

Publication ,  Journal Article
Purev, E; Cai, D; Miller, E; Swoboda, R; Mayer, T; Klein-Szanto, A; Marincola, FM; Mick, R; Otvos, L; Wunner, W; Birebent, B; Somasundaram, R ...
Published in: J Immunol
November 15, 2004

Mutated epidermal growth factor receptor (EGF-RvIII, DeltaEGF-R, and de2-7 EGF-R) is the result of an 801-bp deletion within the extracellular domain of wild-type EGF-R and is expressed by breast carcinomas, but not by normal breast tissues. EGF-RvIII is expressed both on the surface and in the cytoplasm of tumor cells. Thus, EGF-RvIII is a potential tumor-specific target for both Abs and T cells. However, it is not known whether breast cancer patients can raise immune responses to EGF-RvIII expressed by their tumors. The demonstration of EGF-RvIII-specific immune responses in patients would suggest that immunization of patients with EGF-RvIII vaccines is feasible, because these vaccines may boost a pre-existing immune response. We have evaluated humoral and cellular immune responses to EGF-RvIII in 16 breast cancer patients and three healthy donors. Seven of 16 patients developed EGF-RvIII-specific Abs that bound to isolated EGF-RvIII protein or the protein expressed by EGF-RvIII-transfected mouse fibroblasts. The Abs that bound to EGF-RvIII did not bind to wild-type EGF-R, and anti-EGF-RvIII Abs were not found in the sera of healthy donors. Three patients had EGF-RvIII peptide-specific lymphoproliferative responses, and two of these patients also had humoral immune responses. Humoral and cellular immune responses correlated with EGF-RvIII expression by patients' tumors in most cases. These studies demonstrate that breast cancer patients specifically recognize EGF-RvIII with an overall immune response rate of 50%, suggesting that patients may benefit from vaccination against EGF-RvIII, boosting pre-existing immune responses.

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Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

November 15, 2004

Volume

173

Issue

10

Start / End Page

6472 / 6480

Location

United States

Related Subject Headings

  • Sequence Deletion
  • Recombinant Proteins
  • NIH 3T3 Cells
  • Middle Aged
  • Mice
  • Lymphocyte Activation
  • Immunology
  • Humans
  • Female
  • ErbB Receptors
 

Citation

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Purev, E., Cai, D., Miller, E., Swoboda, R., Mayer, T., Klein-Szanto, A., … Herlyn, D. (2004). Immune responses of breast cancer patients to mutated epidermal growth factor receptor (EGF-RvIII, Delta EGF-R, and de2-7 EGF-R). J Immunol, 173(10), 6472–6480. https://doi.org/10.4049/jimmunol.173.10.6472
Purev, Enkhtsetseg, Dewei Cai, Eric Miller, Rolf Swoboda, Ted Mayer, Andres Klein-Szanto, Francesco M. Marincola, et al. “Immune responses of breast cancer patients to mutated epidermal growth factor receptor (EGF-RvIII, Delta EGF-R, and de2-7 EGF-R).J Immunol 173, no. 10 (November 15, 2004): 6472–80. https://doi.org/10.4049/jimmunol.173.10.6472.
Purev E, Cai D, Miller E, Swoboda R, Mayer T, Klein-Szanto A, et al. Immune responses of breast cancer patients to mutated epidermal growth factor receptor (EGF-RvIII, Delta EGF-R, and de2-7 EGF-R). J Immunol. 2004 Nov 15;173(10):6472–80.
Purev, Enkhtsetseg, et al. “Immune responses of breast cancer patients to mutated epidermal growth factor receptor (EGF-RvIII, Delta EGF-R, and de2-7 EGF-R).J Immunol, vol. 173, no. 10, Nov. 2004, pp. 6472–80. Pubmed, doi:10.4049/jimmunol.173.10.6472.
Purev E, Cai D, Miller E, Swoboda R, Mayer T, Klein-Szanto A, Marincola FM, Mick R, Otvos L, Wunner W, Birebent B, Somasundaram R, Wikstrand CJ, Bigner D, DeMichele A, Acs G, Berlin JA, Herlyn D. Immune responses of breast cancer patients to mutated epidermal growth factor receptor (EGF-RvIII, Delta EGF-R, and de2-7 EGF-R). J Immunol. 2004 Nov 15;173(10):6472–6480.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

November 15, 2004

Volume

173

Issue

10

Start / End Page

6472 / 6480

Location

United States

Related Subject Headings

  • Sequence Deletion
  • Recombinant Proteins
  • NIH 3T3 Cells
  • Middle Aged
  • Mice
  • Lymphocyte Activation
  • Immunology
  • Humans
  • Female
  • ErbB Receptors