Clinical and Immunologic Responses of HLA-A3+ Breast Cancer Patients Vaccinated with the HER2/neu-Derived Peptide Vaccine, E75, in a Phase I/II Clinical Trial

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

Research output: Contribution to journalArticle

Abstract

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-A3+, A2- (A3) patients. Study Design: 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. A2-, A3- 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: 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: 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.

Original languageEnglish (US)
Pages (from-to)140-147
Number of pages8
JournalJournal of the American College of Surgeons
Volume210
Issue number2
DOIs
StatePublished - Feb 1 2010
Externally publishedYes

ASJC Scopus subject areas

  • Surgery

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