Journal of Clinical Oncology, Vol 21, Issue 8
(April), 2003: 1562-1573
© 2003 American Society for Clinical Oncology
Adjuvant Immunization of HLA-A2–Positive Melanoma Patients With a Modified gp100 Peptide Induces Peptide-Specific CD8+ T-Cell Responses
John W. Smith, II,
Edwin B. Walker,
Bernard A. Fox,
Daniel Haley,
Ketura P. Wisner,
Teri Doran,
Brenda Fisher,
Lisa Justice,
William Wood,
John Vetto,
Holden Maecker,
Annemiek Dols,
Sybren Meijer,
Hong-Ming Hu,
Pedro Romero,
W. Gregory Alvord,
Walter J. Urba
From the Providence Portland Medical Center, Earle A. Chiles Research Institute, Robert W. Franz Cancer Research Center, and Oregon Health Sciences University, Portland, OR; Ludwig Institute for Cancer Research-Division of Oncology-Immunology, Lausanne, Switzerland; Data Management Services, Frederick Cancer Research and Development Center, National Cancer Institute, Frederick, MD; and Becton-Dickinson Biosciences, San Jose, CA.
Address reprint requests to John W. Smith II, MD, Earle A. Chiles Research Institute, Robert W. Franz Cancer Research Center, Providence Portland Medical Center, 4805 NE Glisan St, 5F40, Portland, OR 97213-2967; email: josmith{at}providence.org.
Purpose: To measure the CD8+ T-cell response to a melanoma peptide vaccine and to compare an every-2-weeks with an every-3-weeks vaccination schedule.
Patients and Methods: Thirty HLA-A2–positive patients with resected stage I to III melanoma were randomly assigned to receive vaccinations every 2 weeks (13 vaccines) or every 3 weeks (nine vaccines) for 6 months. The synthetic, modified gp100 peptide, g209–2M, and a control peptide, HPV16 E7, were mixed in incomplete Freund’s adjuvant and injected subcutaneously. Peripheral blood mononuclear cells obtained before and after vaccination by leukapheresis were analyzed using a fluorescence-based HLA/peptide-tetramer binding assay and cytokine flow cytometry.
Results: Vaccination induced an increase in peptide-specific T cells in 28 of 29 patients. The median frequency of CD8+ T cells specific for the g209–2M peptide increased markedly from 0.02% before to 0.34% after vaccination (P < .0001). Eight patients (28%) exhibited peptide-specific CD8+ T-cell frequencies greater than 1%, including two patients with frequencies of 4.96% and 8.86%, respectively. Interferon alfa-2b–treated patients also had significant increases in tetramer-binding cells (P < .0001). No difference was observed between the every-2-weeks and the every-3-weeks vaccination schedules (P = .59).
Conclusion: Flow cytometric analysis of HLA/peptide-tetramer binding cells was a reliable means of quantifying the CD8+ T-cell response to peptide immunization. This assay may be suitable for use in future trials to optimize different vaccination strategies. Concurrent interferon treatment did not inhibit the development of a peptide-specific immune response and vaccination every 2 weeks, and every 3 weeks produced similar results.
Supported by NIH grant 1R21-CS 82614-01 (W.J.U.), the M.J. Murdock Charitable Trust, and the Chiles Foundation.
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