Adoptive transfer of vaccine-induced peripheral blood mononuclear cells to patients with metastatic melanoma following lymphodepletion

Daniel J. Powell, Mark E. Dudley, Katherine A. Hogan, John R. Wunderlich, Steven A. Rosenberg

Research output: Contribution to journalArticlepeer-review

Abstract

Cancer vaccines can induce the in vivo generation of tumor Ag-specific T cells in patients with metastatic melanoma yet seldom elicit objective clinical responses. Alternatively, adoptive transfer of autologous tumor-infiltrating lymphocytes (TIL) can mediate tumor regression in 50% of lymphodepleted patients, but are logistically and technically difficult to generate. In this study, we evaluated the capability of vaccine-induced PBMC to mediate tumor regression after transfer to patients receiving the same chemotherapy-induced lymphodepletion used for TIL transfer therapy. Aatologous PBMC from nine gp100-vaccinated patients with metastatic melanoma were stimulated ex vivo with the gp100:209-217(210M) peptide and transferred in combination with high-dose IL-2 and cancer vaccine. Transferred PBMC contained highly avid, gp100:209-217 peptide-reactive CD8+ T cells. One week after transfer, lymphocyte counts peaked (median of 14.3 × 103 cells/μl; range of 0.9-59.7 × 103 cells/μl), with 56% of patients experiencing a lymphocytosis. gp100:209-217 peptide-specific CD8+ T cells persisted at high levels in the blood of all patients and demonstrated significant tumor-specific IFN-γ secretion in vitro. Melanocyte-directed autoimmunity was noted in two patients; however, no patient experienced an objective clinical response. These studies demonstrate the feasibility and safety of using vaccine-induced PBMC for cell transfer, but suggests that they are not as effective as TIL in adoptive immunotherapy even when transferred into lymphodepleted hosts.

Original languageEnglish (US)
Pages (from-to)6527-6539
Number of pages13
JournalJournal of Immunology
Volume177
Issue number9
DOIs
StatePublished - Nov 1 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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