Cancer Immunology, Immunotherapy

, Volume 57, Issue 11, pp 1705–1710

Development of a dendritic cell-based vaccine for chronic lymphocytic leukemia

  • M. Palma
  • L. Adamson
  • L. Hansson
  • P. Kokhaei
  • R. Rezvany
  • H. Mellstedt
  • A. Österborg
  • A. Choudhury
Symposium Paper

DOI: 10.1007/s00262-008-0561-y

Cite this article as:
Palma, M., Adamson, L., Hansson, L. et al. Cancer Immunol Immunother (2008) 57: 1705. doi:10.1007/s00262-008-0561-y

Abstract

Evidence for the existence of CLL-specific antigens recognized by the immune system can be gathered from the observation that many patients display monoclonal or oligoclonal expansions and skewed repertoire of T cells. In vitro functional studies have shown that tumor-specific T-cells are able to lyse the leukemic cells. Antileukemic cellular immunity may be boosted in vivo using dendritic cell-based immunotherapy. Our preclinical studies provide evidence that DC that had endocytosed apoptotic CLL cells (Apo-DC) were superior to fusion hybrids, tumor lysate or RNA in eliciting antileukemic T-cell responses in vitro. We have validated a method for enriching the small number of monocyte precursors present in the peripheral blood of CLL patients and utilize them for generating individualized, Apo-DC cellular vaccines. In most cases, a minimum of 50 × 106 Apo-DC could be generated, beginning with immunomagnetically enriched monocytes from a single leukapheresis product containing at least 1% CD14+ cells. Cryopreservation and thawing did not affect the phenotype or the T cell stimulatory function of Apo-DC. A phase I/II, open label clinical trial examining the feasibility, safety and immunogenicity of Apo-DC vaccination has been initiated. CLL patients receive 107 Apo-DC for at least five immunizations and monitored clinically and immunologically for 52 weeks. Three cohorts are accrued stepwise. Cohort I receives Apo-DC alone; Cohort II: Apo-DC+ repeated doses of low-dose GM-CSF; Cohort III: low-dose cyclophosphamide followed by Apo-DC + GM-CSF.

Keywords

CLLDendritic cellT cellImmunotherapyClinical trial

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • M. Palma
    • 1
  • L. Adamson
    • 1
  • L. Hansson
    • 1
  • P. Kokhaei
    • 1
  • R. Rezvany
    • 1
  • H. Mellstedt
    • 2
  • A. Österborg
    • 1
  • A. Choudhury
    • 1
  1. 1.Departments of Oncology and HematologyKarolinska University HospitalStockholmSweden
  2. 2.Department of Oncology (Radiumhemmet)Karolinska University Hospital SolnaStockholmSweden