Phase I/II clinical trial of sequential subcutaneous and intravenous delivery of dendritic cell vaccination for refractory multiple myeloma using patient-specific tumour idiotype protein or idiotype (VDJ)-derived class I-restricted peptides

Antonio Curti, Patrizia Tosi, Patrizia Comoli, Carolina Terragna, Elisa Ferri, Claudia Cellini, Massimo Massaia, Alessandra D'Addio, Valeria Giudice, Cristiana Di Bello, Michele Cavo, Roberto Conte, Gabriele Gugliotta, Michele Baccarani, Roberto M. Lemoli

Research output: Contribution to journalArticle

Abstract

Fifteen multiple myeloma (MM) patients who had failed maintenance therapy after tandem autologous stem cell transplantation underwent anti-idiotype (Id) vaccination with dendritic cells (DCs). CD14+-derived DCs were loaded with the autologous Id as whole protein (=6) or Id-derived class I-restricted peptides (=9) and keyhole limpet hemocyanin (KLH). Vaccination consisted of three subcutaneous (sc) and two intravenous injections of increasing DC doses at 2 weeks interval. DC therapy was well tolerated. Most patients developed both humoral and T-cell responses to KLH, suggesting immunocompetence. Eight of 15 patients developed an Id-specific T-cell proliferative response, 8/15 increased interferon-γ-secreting T cells and 4/15 showed an Id-positive delayed-type hypersensitivity test. Anti-Id cytotoxic T-lymphocyte precursors increased after DC vaccination in 2/2 evaluable patients. A more robust T-cell response was observed after sc DC injections and increased Id-specific T-cell proliferation was found up to 1 year after vaccination. VDJ-derived peptides were as effective as the whole protein in stimulating T-cell responses. Clinically, 7/15 patients have stable disease after a median follow-up of 26 months, one patient achieved durable partial remission after 40 months, and seven patients progressed. In conclusion, sc injections of cryopreserved Id-pulsed DCs were safe and, in contrast with intravenous administrations, induced anti-MM T-cell responses.

Original languageEnglish
Pages (from-to)415-424
Number of pages10
JournalBritish Journal of Haematology
Volume139
Issue number3
DOIs
Publication statusPublished - Nov 2007

Keywords

  • Dendritic cells
  • Idiotype
  • Multiple myeloma
  • T cells
  • Vaccination

ASJC Scopus subject areas

  • Hematology

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