Use of booster inoculations to sustain the clinical effect of an adjuvant breast cancer vaccine

From US Military Cancer Institute Clinical Trials Group Study I-01 and I-02

Authors

  • Jarrod P. Holmes MD,

    1. Department of Hematology and Medical Oncology, Naval Medical Center San Diego, San Diego, California
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  • Guy T. Clifton MD,

    1. Department of Surgery, General Surgery Service, Brooke Army Medical Center, Fort Sam Houston, Texas
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  • Ritesh Patil MD,

    1. Joyce Murtha Breast Cancer Center, Windber, Pennsylvania
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  • Linda C. Benavides MD,

    1. Department of Surgery, General Surgery Service, Brooke Army Medical Center, Fort Sam Houston, Texas
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  • Jeremy D. Gates MD,

    1. Department of Surgery, General Surgery Service, Brooke Army Medical Center, Fort Sam Houston, Texas
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  • Alexander Stojadinovic MD,

    1. Department of Surgery, Walter Reed Army Medical Center, Washington, District of Columbia
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  • Elizabeth A. Mittendorf MD,

    1. Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Sathibalan Ponniah PhD,

    1. Cancer Vaccine Development Program, United States Military Cancer Institute, Bethesda, Maryland
    2. Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland
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  • George E. Peoples MD

    Corresponding author
    1. Department of Surgery, General Surgery Service, Brooke Army Medical Center, Fort Sam Houston, Texas
    2. Cancer Vaccine Development Program, United States Military Cancer Institute, Bethesda, Maryland
    3. Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland
    • Department of Surgery, General Surgery Service, Brooke Army Medical Center, 3851 Roger Brooke Drive, Fort Sam Houston, TX 78234
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    • Fax: (210) 916-6658


  • This article is a U.S. Government work and, as such, is in the public domain in the United States of America.

Abstract

BACKGROUND:

The authors are conducting clinical trials of the HER-2/neu E75-peptide vaccine in clinically disease-free breast cancer (BC) patients. Their phase 1-2 trials revealed that the E75 + granulocyte-macrophage colony-stimulating factor (GM-CSF) vaccine is safe and effective in stimulating clonal expansion of E75-specific CD8+ T cells. They assessed the need for and response to a booster after completion of primary vaccination series.

METHODS:

BC patients enrolled in the E75 vaccine trials who were ≥6 months from completion of their primary vaccination series were offered boosters with E75 + GM-CSF. Patients were monitored for toxicity. E75-specific CD8+ T cells were quantified using the human leukocyte antigen-A2:immunoglobulin G dimer before and after boosting.

RESULTS:

Fifty-three patients received the vaccine booster. Median time from primary vaccination series was 9 months (range, 6-35 months), and median residual E75-specific immunity was 0.70% (range, 0-3.49%) CD8+ lymphocytes. Elevated residual immunity (ERI) (CD8+ E75-specific T cells >0.5%) was seen in 94.4% of patients at 6 months from primary vaccination series versus 48% of patients at >6 months (P = .002). The booster was well tolerated, with only grade 1 and 2 toxicity observed. Local reactions were more robust in patients receiving the booster at 6 months from primary vaccination series compared with those at >6 months (99.4 ± 6.1 mm vs 81.8 ± 4.1 mm, P = .01). In patients lacking ERI, 85% had increased ERI after vaccination (P = .0014).

CONCLUSIONS:

The HER-2/neu E75 peptide vaccine E75 stimulates specific immunity in disease-free BC patients. However, immunity wanes with time. A vaccine booster is safe and effective in stimulating E75-specific immunity in those patients without ERI. These results suggest that the booster may be most effective at 6 months after completion of the primary vaccination series. Cancer 2011. Published 2010 by the American Cancer Society.

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