Vaccination with dendritic cells loaded with tumor apoptotic bodies (Apo-DC) in patients with chronic lymphocytic leukemia: Effects of various adjuvants and definition of immune response criteria

Palma, Marzia, Hansson, Lotta, Choudhury, Aniruddha, Nasman-Glaser, Barbro, Eriksson, Ingrid, Adamson, Lars, Rossmann, Eva, Widen, Karin, Horvath, Rudolf, Kokhaei, Parviz, Vertuani, Simona, Mellstedt, Hakan and Osterborg, Anders (2012) Vaccination with dendritic cells loaded with tumor apoptotic bodies (Apo-DC) in patients with chronic lymphocytic leukemia: Effects of various adjuvants and definition of immune response criteria. Cancer Immunology Immunotherapy, 61 6: 865-879. doi:10.1007/s00262-011-1149-5


Author Palma, Marzia
Hansson, Lotta
Choudhury, Aniruddha
Nasman-Glaser, Barbro
Eriksson, Ingrid
Adamson, Lars
Rossmann, Eva
Widen, Karin
Horvath, Rudolf
Kokhaei, Parviz
Vertuani, Simona
Mellstedt, Hakan
Osterborg, Anders
Title Vaccination with dendritic cells loaded with tumor apoptotic bodies (Apo-DC) in patients with chronic lymphocytic leukemia: Effects of various adjuvants and definition of immune response criteria
Journal name Cancer Immunology Immunotherapy   Check publisher's open access policy
ISSN 0340-7004
1432-0851
Publication date 2012-06
Year available 2011
Sub-type Article (original research)
DOI 10.1007/s00262-011-1149-5
Volume 61
Issue 6
Start page 865
End page 879
Total pages 15
Place of publication Heidelberg, Germany
Publisher Springer
Collection year 2013
Language eng
Formatted abstract We previously demonstrated that autologous dendritic cells that have endocytosed apoptotic bodies of chronic lymphocytic leukemia (CLL) cells (Apo-DC) can stimulate antileukemic T cell responses in vitro. In this phase I study, we vaccinated 15 asymptomatic CLL patients at five time points with Apo-DC administered intradermally either alone (cohort I), or in combination with subcutaneous granulocyte-macrophage-colony-stimulating-factor (GM-CSF) (cohort II) or with GM-CSF and intravenous low-dose cyclophosphamide (cohort III). Aim of the study was to evaluate the safety and immunogenicity of Apo-DC alone or in combination with GM-CSF and low-dose cyclophosphamide in CLL patients. All patients completed the vaccination schedule without dose-limiting toxicity. No objective clinical responses were seen. Vaccine-induced leukemia-specific immune responses were evaluated by IFN-γ ELISpot and proliferation assays over a 52 weeks observation period and immune response criteria were defined. According to these criteria, 10/15 patients were defined as immune responders. The frequency of immune-responding patients was higher in cohorts II (3/5) and III (5/5) than in cohort I (2/5). In order to further characterize the induced immune response, estimation of secreted cytokines and CD107-degranulation assay were performed. Clustering of T and CLL cells was observed in CD107-degranulation assay and visualized by confocal microscopy. Additionally, assessment of regulatory T cells (T regs) revealed their significantly lower frequencies in immune responders versus non-responders (P < 0.0001). Cyclophosphamide did not reduce T regs frequency. In conclusion, vaccination with Apo-DC + GM-CSF and cyclophosphamide was safe and elicited anti-CLL immune responses that correlated inversely with T regs levels. Lack of clinical responses highlights the necessity to develop more potent vaccine strategies in B cell malignancies.
Keyword CLL
Dendritic cells
Immunotherapy
Cyclophosphamide
Regulatory T cells
GM-CSF
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online: 16 November 2011

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
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