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Effect of Dose on Immune Response in Patients Vaccinated With an HER-2/neu Intracellular Domain Protein—Based Vaccine

From the Tumor Vaccine Group, Oncology, University of Washington; Fred Hutchinson Cancer Research Center; and Corixa Corporation, Seattle, WA.

Address reprint requests to Mary L. Disis, MD, Tumor Vaccine Group, Oncology, Box 356527, University of Washington, Seattle, WA 98195-6527; e-mail: ndisis{at}u.washington.edu

PURPOSE: To evaluate the safety of an HER-2/neu intracellular domain (ICD) protein vaccine and to estimate whether vaccine dose impacts immunogenicity.

PATIENTS AND METHODS: Twenty-nine patients with HER-2/neu—overexpressing breast or ovarian cancer and with no evidence of disease after standard therapy received a low- (25 µg), intermediate- (150 µg), or high-dose (900 µg) HER-2/neu ICD protein vaccine. The vaccine was administered intradermally, monthly for 6 months, with granulocyte-macrophage colony-stimulating factor as an adjuvant. Toxicity and both cellular and humoral HER-2/neu—specific immunity was evaluated.

RESULTS: The vaccine was well tolerated. The majority of patients (89%) developed HER-2/neu ICD-specific T-cell immunity. The dose of vaccine did not predict the magnitude of the T-cell response. The majority of patients (82%) also developed HER-2/neu—specific immunoglobulin G antibody immunity. Vaccine dose did not predict magnitude or avidity of the HER-2/neu—specific humoral immune response. Time to development of detectable HER-2/neu—specific immunity, however, was significantly earlier for the high- versus low-dose vaccine group (P = .003). Over half the patients retained HER-2/neu—specific T-cell immunity 9 to 12 months after immunizations had ended.

CONCLUSION: The HER-2/neu ICD protein vaccine was well tolerated and effective in eliciting HER-2/neu—specific T-cell and antibody immunity in the majority of breast and ovarian cancer patients who completed the vaccine regimen. Although the dose of vaccine did not impact the magnitude of T-cell or antibody immunity elicited, patients receiving the highest dose developed HER-2/neu—specific immunity more rapidly than those who received the lowest dose.

Supported by grants from the Cancer Research Treatment Foundation and the National Institutes of Health (NIH), National Cancer Institute grant No. U54-CA090818 (M.L.D), by NIH training grant No. T32 (HL07093; L.G.S.), and by a fellowship from the Department of Defense Breast Cancer Program (DAMD 17-00-1-0492; K.L.K.). Patient care was conducted through the Clinical Research Center Facility at the University of Washington, which is supported through NIH grant No. MO1-RR-00037.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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