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 Immunol Immunother. 2012 Jun;61(6):865-79. doi: 10.1007/s00262-011-1149-5. Epub 2011 Nov 16.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic*
  • Adult
  • Aged
  • Apoptosis / immunology*
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Cell-Derived Microparticles / immunology*
  • Cyclophosphamide / immunology
  • Cyclophosphamide / pharmacology
  • Dendritic Cells / immunology*
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Leukemia, Lymphocytic, Chronic, B-Cell / therapy*
  • Male
  • Middle Aged
  • Vaccination*


  • Adjuvants, Immunologic
  • Cancer Vaccines
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Cyclophosphamide