Original Article
Leukemia (2008) 22, 1007–1017; doi:10.1038/leu.2008.29; published online 6 March 2008
Immunology
Vaccination of B-CLL patients with autologous dendritic cells can change the frequency of leukemia antigen-specific CD8+ T cells as well as CD4+CD25+FoxP3+ regulatory T cells toward an antileukemia response
I Hus1,4, M Schmitt2,4, J Tabarkiewicz3, S Radej3, K Wojas2,3, A Bojarska-Junak3, A Schmitt2, K Giannopoulos3, A Dmoszy
ska1 and J Roli
ski3
- 1Department of Hematooncology, Medical University of Lublin, Lublin, Poland
- 2Department of Internal Medicine III, University of Ulm, Ulm, Germany
- 3Department of Clinical Immunology, Medical University of Lublin, Lublin, Poland
Correspondence: Professor M Schmitt, Department of Internal Medicine III, University of Ulm, Robert-Koch-Str. 8, Ulm 89081, Germany. E-mail: michael.schmitt@uniklinik-ulm.de
4These authors contributed equally to this work
Received 26 November 2007; Revised 16 January 2008; Accepted 28 January 2008; Published online 6 March 2008.
Abstract
Recently, we described that vaccination with allogeneic dendritic cells (DCs) pulsed with tumor cell lysate generated specific CD8+ T cell response in patients with B-cell chronic lymphocytic leukemia (B-CLL). In the present study, the potential of autologous DCs pulsed ex vivo with tumor cell lysates to stimulate antitumor immunity in patients with B-CLL in early stages was evaluated. Twelve patients at clinical stage 0–2 as per Rai were vaccinated intradermally up to eight times with a mean number of 7.4
106 DCs pulsed with B-CLL cell lysate. We observed a decrease of peripheral blood leukocytes and CD19+/CD5+ leukemic cells in five patients, three patients showed a stable disease and four patients progressed despite DC vaccination. A significant increase of specific cytotoxic CD8+ T lymphocytes against the leukemia-associated antigens RHAMM or fibromodulin was detected in four patients after DC vaccination. In patients with a clinical response, an increase of interleukin 12 (IL-12) serum levels and a decrease of the frequency of CD4+CD25+FOXP3+ T regulatory cells were observed. Taken together, the study demonstrated that vaccination with autologous DC in CLL patients is feasible and safe. Immunological and to some extend hematological responses could be noted, justifying further investigation on this immunotherapeutical approach.
Keywords:
chronic lymphocytic leukemia, immunotherapy, RHAMM/CD168, dendritic cells, tumor cell lysates, magnetic cell separation
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