Semnan University of Medical Sciences

Research and Technology Vice Chancellor

Palma, Marzia and Hansson, Lotta and Choudhury, Aniruddha and Näsman-Glaser, Barbro and Eriksson, Ingrid and Adamson, Lars and Rossmann, Eva and Widén, Karin and Horváth, Rudolf and Kokhaei, Parviz and Vertuani, Simona and Mellstedt, Håkan and Österborg, 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). pp. 865-879. ISSN 0340-7004

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    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.

    Item Type: Article
    Subjects: R Medicine > R Medicine (General)
    Divisions: Faculty of Medical Sciences > School of Medicine
    Depositing User: Mr Vahab Moshtaghi
    Date Deposited: 26 Nov 2016 07:38
    Last Modified: 26 Nov 2016 07:38
    URI: http://eprints.semums.ac.ir/id/eprint/519

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