Details

Autor(en) / Beteiligte

• Purev, Enkhtsetseg
• Cai, Dewei
• Miller, Eric
• Swoboda, Rolf
• Mayer, Ted
• Klein-Szanto, Andres
• Marincola, Francesco M
• Mick, Rosemarie
• Otvos, Laszlo
• Wunner, William
• Birebent, Brigitte
• Somasundaram, Rajasekharan
• Wikstrand, Carol J
• Bigner, Darell
• DeMichele, Angela
• Acs, Geza
• Berlin, Jesse A
• Herlyn, Dorothee

Titel

Immune Responses of Breast Cancer Patients to Mutated Epidermal Growth Factor Receptor (EGF-RvIII, {Delta}EGF-R, and de2-7 EGF-R)

Ist Teil von

• The Journal of immunology (1950), 2004-11, Vol.173 (10), p.6472-6480

Ort / Verlag

United States: Am Assoc Immnol

Erscheinungsjahr

2004

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.