Journal of the American College of Surgeons
Volume 210, Issue 2 , Pages 140-147, February 2010

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, MD

      Affiliations

    • Joyce Murtha Breast Care Center, Windber Medical Center, Windber, PA
    • ,
  • Guy T. Clifton, MD

      Affiliations

    • Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, TX
    • ,
  • Jarrod P. Holmes, MD

      Affiliations

    • Department of Hematology and Medical Oncology, Naval Medical Center, San Diego, CA
    • ,
  • Asna Amin, MD

      Affiliations

    • Cancer Vaccine Development Program, United States Military Cancer Institute, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD
    • ,
  • Mark G. Carmichael, MD

      Affiliations

    • Cancer Vaccine Development Program, United States Military Cancer Institute, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD
    • ,
  • Jeremy D. Gates, MD

      Affiliations

    • Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, TX
    • ,
  • Linda H. Benavides, MD

      Affiliations

    • Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, TX
    • ,
  • Matthew T. Hueman, MD

      Affiliations

    • Cancer Vaccine Development Program, United States Military Cancer Institute, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD
    • ,
  • Sathibalan Ponniah, PhD

      Affiliations

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

      Affiliations

    • Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, TX
    • Cancer Vaccine Development Program, United States Military Cancer Institute, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD
    • Corresponding Author InformationCorrespondence address: col George E Peoples, md, facs, Department of Surgery, General Surgery Service, Brooke Army Medical Center, 3851 Roger Brooke Dr, Fort Sam Houston, TX 78234

Received 26 August 2009; received in revised form 20 October 2009; accepted 21 October 2009. published online 21 December 2009.

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.

Abbreviations and Acronyms: CTL, cytotoxic T lymphocyte, DTH, delayed-type hypersensitivity, ELISPOT, enzyme-linked immunosorbent spot assay, GM-CSF, granulocyte-macrophage colony-stimulating factor, IFN, interferon, NN, node-negative, NP, node-positive, PBMC, peripheral blood mononuclear cells, TAA, tumor-associated antigen

To access this article, please choose from the options below

Login to an existing account or Register a new account.

  • Purchase this article for 31.50 USD (You must login/register to purchase this article)

    Online access for 24 hours. The PDF version can be downloaded as your permanent record.

  • Subscribe to this title

    Get unlimited online access to this article and all other articles in this title 24/7 for one year.

  • Claim access now

    For current subscribers with Society Membership or Account Number.

  • Visit SciVerse ScienceDirect to see if you have access via your institution.
 

 Disclosure Information: Dr Peoples holds patent rights to the E75 vaccine.

 This study was supported by the United States Military Cancer Institute, Department of Surgery, Uniformed Services University of the Health Sciences, and the Department of Clinical Investigation, Walter Reed Army Medical Center, Bethesda, MD.

 This article represents the personal viewpoint of the authors and cannot be construed as a statement of official Department of the Army, Department of the Navy, or Department of Defense policy.

PII: S1072-7515(09)01557-9

doi:10.1016/j.jamcollsurg.2009.10.022

Journal of the American College of Surgeons
Volume 210, Issue 2 , Pages 140-147, February 2010

Article Tools

* Image Usage & Resolution