Adjuvant immunization of HLA-A2-positive melanoma patients with a modified gp100 peptide induces peptide-specific CD8+ T-cell responses

John W. Smith, 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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1562-1573
Number of pages12
JournalJournal of Clinical Oncology
Volume21
Issue number8
DOIs
StatePublished - Apr 15 2003
Externally publishedYes

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HLA-A2 Antigen
Melanoma
Immunization
Vaccination
T-Lymphocytes
Peptides
interferon alfa-2b
Appointments and Schedules
Vaccines
Peptide T
Leukapheresis
Subunit Vaccines
Interferons
Blood Cells
Flow Cytometry
Fluorescence
Cytokines

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Adjuvant immunization of HLA-A2-positive melanoma patients with a modified gp100 peptide induces peptide-specific CD8+ T-cell responses. / Smith, John W.; Walker, Edwin B.; Fox, Bernard A.; Haley, Daniel; Wisner, Ketura P.; Doran, Teri; Fisher, Brenda; Justice, Lisa; Wood, William; Vetto, John; Maecker, Holden; Dols, Annemiek; Meijer, Sybren; Hu, Hong Ming; Romero, Pedro; Alvord, W. Gregory; Urba, Walter J.

In: Journal of Clinical Oncology, Vol. 21, No. 8, 15.04.2003, p. 1562-1573.

Research output: Contribution to journalArticle

Smith, JW, Walker, EB, Fox, BA, Haley, D, Wisner, KP, Doran, T, Fisher, B, Justice, L, Wood, W, Vetto, J, Maecker, H, Dols, A, Meijer, S, Hu, HM, Romero, P, Alvord, WG & Urba, WJ 2003, 'Adjuvant immunization of HLA-A2-positive melanoma patients with a modified gp100 peptide induces peptide-specific CD8+ T-cell responses', Journal of Clinical Oncology, vol. 21, no. 8, pp. 1562-1573. https://doi.org/10.1200/JCO.2003.09.020
Smith, John W. ; Walker, Edwin B. ; Fox, Bernard A. ; Haley, Daniel ; Wisner, Ketura P. ; Doran, Teri ; Fisher, Brenda ; Justice, Lisa ; Wood, William ; Vetto, John ; Maecker, Holden ; Dols, Annemiek ; Meijer, Sybren ; Hu, Hong Ming ; Romero, Pedro ; Alvord, W. Gregory ; Urba, Walter J. / Adjuvant immunization of HLA-A2-positive melanoma patients with a modified gp100 peptide induces peptide-specific CD8+ T-cell responses. In: Journal of Clinical Oncology. 2003 ; Vol. 21, No. 8. pp. 1562-1573.
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abstract = "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.",
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T1 - Adjuvant immunization of HLA-A2-positive melanoma patients with a modified gp100 peptide induces peptide-specific CD8+ T-cell responses

AU - Smith, John W.

AU - Walker, Edwin B.

AU - Fox, Bernard A.

AU - Haley, Daniel

AU - Wisner, Ketura P.

AU - Doran, Teri

AU - Fisher, Brenda

AU - Justice, Lisa

AU - Wood, William

AU - Vetto, John

AU - Maecker, Holden

AU - Dols, Annemiek

AU - Meijer, Sybren

AU - Hu, Hong Ming

AU - Romero, Pedro

AU - Alvord, W. Gregory

AU - Urba, Walter J.

PY - 2003/4/15

Y1 - 2003/4/15

N2 - 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.

AB - 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.

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