Clinical and Immunologic Responses of HLA-A3p>+p> Breast Cancer Patients Vaccinated with the HER2/neu-Derived Peptide Vaccine, E75, in a Phase I/II Clinical Trial

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• 作者：Ritesh Patil ; Guy T. Clifton ; Jarrod P. Holmes ; Asna Amin ; Mark G. Carmichael ; Jeremy D. Gates ; Linda H. Benavides ; Matthew T. Hueman ; Sathibalan Ponniah ; George E. Peoples
• 刊名：Journal of the American College of Surgeons
• 出版年：2010
• 出版时间：February 2010
• 年：2010
• 卷：210
• 期：2
• 页码：140-147
• 全文大小：727 K

文摘

Background

We have treated disease-free breast cancer patients with an HER2/neu-derived peptide, E75, as an adjuvant vaccine. E75 was originally described as HLA-A2−restricted and has been previously tested in this population. Based on computer modeling, E75 is predicted to bind to HLA-A3, and preclinical data support this. We conducted a clinical trial of E75 in HLA-A3p>+p>, A2p>−p> (A3) patients.

Study Design

<p>Disease-free breast cancer patients were enrolled after standard therapy in phase I/II trials. A3 patients were enrolled in parallel with A2 patients and vaccinated with E75 and granulocyte-macrophage colony-stimulating factor immunoadjuvant. A2p>−p>, A3p>−p> patients were followed as controls. Toxicities were graded. Immunologic responses were assessed by delayed-type hypersensitivity reactions and E75-specific interferon-γ enzyme-linked immunosorbent spot assay. Clinical recurrences were documented.

Results

<p>Thirteen A3 patients completed the vaccine schedule. Clinicopathologic features were similar between A3, A2, and control patients, except for more HER2/neu-overexpressing tumors in the A2 group and more estrogen-receptor/progesterone-receptor−negative tumors in A2 and A3 groups. Toxicity profiles and postvaccination delayed-type hypersensitivity were similar in A3 and A2 patients. Enzyme-linked immunosorbent spot assay results varied, but A3 patients' median spots increased pre- to postvaccination (p = 0.2). Recurrences were lower in the A3 group (7.7 % ) at 30-month median follow-up compared with published recurrence in A2-vaccinated (8.3 % ) and control groups (14.8 % ) at 26-month median follow-up.

Conclusions

<p>HLA restriction limits potential use of peptide-based cancer vaccines. This trial demonstrates that HLA-A3 patients respond similarly to E75 vaccination as HLA-A2 patients, suggesting the potential use of the E75 vaccine in up to 76 % of the population.