Immune responses of breast cancer patients to mutated epidermal growth factor receptor (EGF-RvIII, Delta EGF-R, and de2-7 EGF-R).
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.
Purev
Enkhtsetseg
E
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Cai
Dewei
D
Miller
Eric
E
Swoboda
Rolf
R
Mayer
Ted
T
Klein-Szanto
Andres
A
Marincola
Francesco M
FM
Mick
Rosemarie
R
Otvos
Laszlo
L
Wunner
William
W
Birebent
Brigitte
B
Somasundaram
Rajasekharan
R
Wikstrand
Carol J
CJ
Bigner
Darell
D
DeMichele
Angela
A
Acs
Geza
G
Berlin
Jesse A
JA
Herlyn
Dorothee
D
D000328:Adult; D000368:Aged; D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis / Q000378:metabolism; D001666:Binding Sites, Antibody / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008875:Middle Aged; D041681:NIH 3T3 Cells; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion
D000912:Antibodies, Neoplasm; D011994:Recombinant Proteins; D066246:ErbB Receptors