TY - JOUR
T1 - Evaluation of the HER2/neu-derived peptide GP2 for use in a peptide-based breast cancer vaccine trial
AU - Mittendorf, Elizabeth A.
AU - Storrer, Catherine E.
AU - Foley, Rebecca J.
AU - Harris, Katie
AU - Jama, Yusuf
AU - Shriver, Craig D.
AU - Ponniah, Sathibalan
AU - Peoples, George E.
PY - 2006/6/1
Y1 - 2006/6/1
N2 - BACKGROUND. E75 and GP2 are human leukocyte antigen (HLA)-A2-restricted immunogenic peptides derived from the HER2/neu protein. In a E75 peptide-based vaccine trial, preexisting immunity and epitope spreading to GP2 was detected. The purpose of this study was to further investigate GP2 for potential use in vaccination strategies. Importantly, a naturally occurring polymorphism (I → V at position 2, 2VGP2) associated with increased breast cancer risk was addressed. METHODS. Prevaccination peripheral blood samples (PBMC) from HLA-A2 breast cancer patients and CD8+ T cells from HLA-A2 healthy donors were stimulated with autologous dendritic cells (DC) pulsed with GP2 and tested in standard cytotoxicity assays with HER2/neu+ tumor cells or GP2- or 2VGP2-loaded T2 targets. Additional cytotoxicity experiments used effectors stimulated with DC pulsed with E75, GP2, or the combination of E75 + GP2. RESULTS. GP2-stimulated prevaccination PBMC from 28 patients demonstrated killing of MCF-7, SKOV3-A2, and the HLA-A2- control target SKOV3 of 28.8 ± 3.7% (P<.01), 29.5 ± 4.0% (P<.01), and 16.9 ± 2.7%, respectively. When compared with E75, GP2-stimulated CD8+ T cells lysed HER2/neu+ targets at 43.8 ± 5.2% versus 44.2 ± 5.7% for E75 (P = .87). When combined, an additive effect was noted with 58.6 ± 5.4% lysis (P = .05). GP2-stimulated CD8+ T cells specifically recognized both GP2-loaded (19.6 ± 5.7%) and 2VGP2-loaded T2 targets (17.7 ± 5.2%). CONCLUSIONS. GP2 is a clinically relevant HER2/neu-derived peptide with immunogenicity comparable to that of E75. Importantly, GP2-specific effectors recognize 2VGP2-expressing targets; therefore, a GP2 vaccine should be effective in patients carrying this polymorphism. GP2 may be most beneficial used in a multiepitope vaccine.
AB - BACKGROUND. E75 and GP2 are human leukocyte antigen (HLA)-A2-restricted immunogenic peptides derived from the HER2/neu protein. In a E75 peptide-based vaccine trial, preexisting immunity and epitope spreading to GP2 was detected. The purpose of this study was to further investigate GP2 for potential use in vaccination strategies. Importantly, a naturally occurring polymorphism (I → V at position 2, 2VGP2) associated with increased breast cancer risk was addressed. METHODS. Prevaccination peripheral blood samples (PBMC) from HLA-A2 breast cancer patients and CD8+ T cells from HLA-A2 healthy donors were stimulated with autologous dendritic cells (DC) pulsed with GP2 and tested in standard cytotoxicity assays with HER2/neu+ tumor cells or GP2- or 2VGP2-loaded T2 targets. Additional cytotoxicity experiments used effectors stimulated with DC pulsed with E75, GP2, or the combination of E75 + GP2. RESULTS. GP2-stimulated prevaccination PBMC from 28 patients demonstrated killing of MCF-7, SKOV3-A2, and the HLA-A2- control target SKOV3 of 28.8 ± 3.7% (P<.01), 29.5 ± 4.0% (P<.01), and 16.9 ± 2.7%, respectively. When compared with E75, GP2-stimulated CD8+ T cells lysed HER2/neu+ targets at 43.8 ± 5.2% versus 44.2 ± 5.7% for E75 (P = .87). When combined, an additive effect was noted with 58.6 ± 5.4% lysis (P = .05). GP2-stimulated CD8+ T cells specifically recognized both GP2-loaded (19.6 ± 5.7%) and 2VGP2-loaded T2 targets (17.7 ± 5.2%). CONCLUSIONS. GP2 is a clinically relevant HER2/neu-derived peptide with immunogenicity comparable to that of E75. Importantly, GP2-specific effectors recognize 2VGP2-expressing targets; therefore, a GP2 vaccine should be effective in patients carrying this polymorphism. GP2 may be most beneficial used in a multiepitope vaccine.
KW - Breast cancer
KW - GP2
KW - HER2/neu
KW - Peptide vaccine
UR - http://www.scopus.com/inward/record.url?scp=33646886582&partnerID=8YFLogxK
U2 - 10.1002/cncr.21849
DO - 10.1002/cncr.21849
M3 - Article
C2 - 16596621
AN - SCOPUS:33646886582
SN - 0008-543X
VL - 106
SP - 2309
EP - 2317
JO - Cancer
JF - Cancer
IS - 11
ER -