In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 23, No. 30 ( 2005-10-20), p. 7536-7545
Abstract:
E75 is an immunogenic peptide from the HER2/neu protein that is highly expressed in breast cancer. We are conducting a clinical trial of an E75 + granulocyte-macrophage colony-stimulating factor vaccine to assess safety, immunologic response, and the prevention of clinical recurrences in patients with disease-free, node-positive breast cancer (NPBC). Patients and Methods Fifty-three patients with NPBC were enrolled and HLA typed. HLA-A2 + patients (n = 24) were vaccinated, and HLA-A2 − patients (n = 29) are observed prospectively as clinical controls. Local/systemic toxicities, immunologic responses, and time to recurrence are being measured. Results Only minor toxicities have occurred (one grade 3 [4%]). All patients have demonstrated clonal expansion of E75-specific CD8 + T cells that lysed HER2/neu-expressing tumor cells. An optimal dosage and schedule have been established. Patients have developed delayed-type hypersensitivity reactions to E75 postvaccination compared with controls (33 v 7 mm; P 〈 .01). HLA-A2 + patients have been found to have larger, more poorly differentiated, and more hormonally insensitive tumors compared to HLA-A2 − patients. Despite this, the only two deaths have occurred in the control group. The disease-free survival in the vaccinated group is 85.7% compared to 59.8% in the controls at 22 months' median follow-up with a recurrence rate of 8% compared to 21%, respectively (P 〈 .19). Median time to recurrence in the vaccinated patients was prolonged (11 v 8 months), and recurrence correlated with a weak delayed-type hypersensitivity response. Conclusion This HER2/neu (E75) vaccine is safe and effective in eliciting a peptide-specific immune response in vivo. Induced HER2/neu immunity seems to reduce the recurrence rate in patients with NPBC.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2005.03.047
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2005
detail.hit.zdb_id:
2005181-5
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