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

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Abstract
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.