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

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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

Fingerprint

Phase II Clinical Trials
Clinical Trials, Phase I
Multiple Myeloma
Dendritic Cells
Vaccination
T-Lymphocytes
Peptides
Neoplasms
Proteins
Immunocompetence
Delayed Hypersensitivity
Stem Cell Transplantation
Cytotoxic T-Lymphocytes
Subcutaneous Injections
Cell- and Tissue-Based Therapy
Intravenous Injections
Intravenous Administration
Interferons
Cell Proliferation
Injections

Keywords

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

ASJC Scopus subject areas

  • Hematology

Cite this

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

In: British Journal of Haematology, Vol. 139, No. 3, 11.2007, p. 415-424.

Research output: Contribution to journalArticle

Curti, Antonio ; Tosi, Patrizia ; Comoli, Patrizia ; Terragna, Carolina ; Ferri, Elisa ; Cellini, Claudia ; Massaia, Massimo ; D'Addio, Alessandra ; Giudice, Valeria ; Di Bello, Cristiana ; Cavo, Michele ; Conte, Roberto ; Gugliotta, Gabriele ; Baccarani, Michele ; Lemoli, Roberto M. / 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. In: British Journal of Haematology. 2007 ; Vol. 139, No. 3. pp. 415-424.
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AU - Tosi, Patrizia

AU - Comoli, Patrizia

AU - Terragna, Carolina

AU - Ferri, Elisa

AU - Cellini, Claudia

AU - Massaia, Massimo

AU - D'Addio, Alessandra

AU - Giudice, Valeria

AU - Di Bello, Cristiana

AU - Cavo, Michele

AU - Conte, Roberto

AU - Gugliotta, Gabriele

AU - Baccarani, Michele

AU - Lemoli, Roberto M.

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