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

Abstract

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.

• Authors: Enkhtsetseg Purev, Dewei Cai, Eric Miller, Rolf Swoboda, Ted Mayer, Andres Klein-Szanto, Francesco M Marincola, Rosemarie Mick, Laszlo Otvos, William Wunner, Brigitte Birebent, Rajasekharan Somasundaram, Carol J Wikstrand, Darell Bigner, Angela DeMichele, Geza Acs, Jesse A Berlin, Dorothee Herlyn
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 173 Issue 10 Pg. 6472-80 (Nov 15 2004) ISSN: 0022-1767 [Print] United States
• PMID: 15528389 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Neoplasm
• Recombinant Proteins
• ErbB Receptors

Topics

• Adult
• Aged
• Animals
• Antibodies, Neoplasm (biosynthesis, metabolism)
• Binding Sites, Antibody (genetics)
• Breast Neoplasms (genetics, immunology, metabolism)
• Cell Line
• Cell Line, Transformed
• Cell Line, Tumor
• ErbB Receptors (biosynthesis, genetics, immunology, metabolism)
• Female
• Humans
• Lymphocyte Activation (genetics, immunology)
• Mice
• Middle Aged
• NIH 3T3 Cells
• Recombinant Proteins (biosynthesis, genetics, metabolism)
• Sequence Deletion