Immunization of HLA-A*0201 and/or HLA-DPβ1*04 patients with metastatic melanoma using epitopes from the NY-ESO-1 antigen

Hung T. Khong, James C. Yang, Suzanne Topalian, Richard M. Sherry, Sharon A. Mavroukakis, Donald E. White, Steven A. Rosenberg

Research output: Contribution to journalArticle

Abstract

HLA class I-restricted peptides are often used in peptide vaccine regimens. There is strong evidence that many of these peptides can generate specific CD8+ T-cell responses in vivo; however, only occasional objective clinical responses have been reported. To test whether provision of "help" would enhance antitumor immunity, the authors initiated a clinical trial in which patients with metastatic melanoma were immunized against the NY-ESO-1 tumor antigen, using an HLA-A2-restricted peptide (ESO-1:165V), an HLA-DP4-restricted peptide (NY-ESO-1:161-180), or both peptides given concomitantly. The first cohorts received only ESO-1:165V, using three vaccination schedules. Immunologically, most patients developed immune responses to the HLA-A2-restricted native ESO-1 epitope after vaccination. Peptide vaccine given daily for 4 days appeared to induce immunologic responses more rapidly than if given once a week or once every 3 weeks. In contrast, vaccination using the NY-ESO-1:161-180 peptide induced immune responses in only a few patients. Clinically, one patient who received NY-ESO-1:161-180 peptide alone had a partial response lasing 12 months. Concomitant vaccination with the HLA class II-restricted peptide did not alter the immune response to the HLA class I-restricted peptide form NY-ESO-1. However, vaccination with the HLA-A2-restricted epitope generated primarily T cells that did not recognize tumor after in vitro sensitization. This result raises questions about the use of synthetic peptides derived from NY-ESO-1 as a sole form of immunization.

Original languageEnglish (US)
Pages (from-to)472-477
Number of pages6
JournalJournal of Immunotherapy
Volume27
Issue number6
StatePublished - Nov 2004
Externally publishedYes

Fingerprint

Epitopes
Melanoma
Immunization
Antigens
Peptides
Vaccination
HLA-A2 Antigen
Subunit Vaccines
HLA-A*02:01 antigen
HLA-DPw1 antigen
T-Lymphocytes
Neoplasm Antigens
Immunity
Appointments and Schedules
Clinical Trials

Keywords

  • Cancer vaccine
  • HLA-A2
  • HLA-DP
  • NY-ESO-1
  • Tumor antigens

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

Cite this

Khong, H. T., Yang, J. C., Topalian, S., Sherry, R. M., Mavroukakis, S. A., White, D. E., & Rosenberg, S. A. (2004). Immunization of HLA-A*0201 and/or HLA-DPβ1*04 patients with metastatic melanoma using epitopes from the NY-ESO-1 antigen. Journal of Immunotherapy, 27(6), 472-477.

Immunization of HLA-A*0201 and/or HLA-DPβ1*04 patients with metastatic melanoma using epitopes from the NY-ESO-1 antigen. / Khong, Hung T.; Yang, James C.; Topalian, Suzanne; Sherry, Richard M.; Mavroukakis, Sharon A.; White, Donald E.; Rosenberg, Steven A.

In: Journal of Immunotherapy, Vol. 27, No. 6, 11.2004, p. 472-477.

Research output: Contribution to journalArticle

Khong, HT, Yang, JC, Topalian, S, Sherry, RM, Mavroukakis, SA, White, DE & Rosenberg, SA 2004, 'Immunization of HLA-A*0201 and/or HLA-DPβ1*04 patients with metastatic melanoma using epitopes from the NY-ESO-1 antigen', Journal of Immunotherapy, vol. 27, no. 6, pp. 472-477.
Khong, Hung T. ; Yang, James C. ; Topalian, Suzanne ; Sherry, Richard M. ; Mavroukakis, Sharon A. ; White, Donald E. ; Rosenberg, Steven A. / Immunization of HLA-A*0201 and/or HLA-DPβ1*04 patients with metastatic melanoma using epitopes from the NY-ESO-1 antigen. In: Journal of Immunotherapy. 2004 ; Vol. 27, No. 6. pp. 472-477.
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