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Clinical and Immunological Effects in Patients with.Advanced Non-Small Cell Lung-Cancer after Vaccination with.Dendritic Cells Exposed to an Allogeneic Tumor Cell Lysate

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World Journal of Vaccines 2013年第2期3卷 68-76页

作者： Lotte Engell-Noerregaard Pia Kvistborg Mai-Britt Zocca Ayako W. Pedersen mogens h. claesson Anders Mellemgaard DanDrit Biotech.A/S Copenhagen Denmark Department of International h.alth Immunology and Microbiology The Panum Institute University of Copenhagen Copenhagen Denmark Department of Oncology Herlev University Hospital Herlev Denmark

Background: We evaluated th. clinical and immunological effects of dendritic cell (DC) vaccination of patients with.NSCLC. Autologous DCs were pulsed with.a MAGE containing allogeneic melanoma cell lysate (MelCancerVac?, Dandrit Biotech.Copenh.gen,Denmark). Imiquimod cream, proleukin and celecoxib were used as adjuvants to th. vaccines. Th. objective of th. study was to evaluate specific T cell response in vitro by IFNg EliSpot. Secondary objectives were overall survival, response and quality of life (QoL). Results: Twenty-two patients initiated th. vaccination program consisting of ten vaccinations. Seven patients remained in stable disease (SD) th.ee month. after th. first vaccination. After ten vaccinations (six month.), four patients still sh.wed SD and continued vaccinations on a month.y basis. Th.se four patients received a total of 12, 16, 26 and 35 vaccinations, respectively. Five patients sh.wed an unexpectedly prolonged survival. Th. treatment was well tolerated and only minor adverse events were reported. Quality of life did not ch.nge during th. study period. In four of th. seven patients with.SD, vaccine-specific T cells were detected by IFNγ EliSpot assays, wh.reas only one patient with.progressive disease (PD) sh.wed vaccine-specific responses. Conclusion: Th.s DC-based vaccine trial h.s indicated a correlation between vaccine-specific immunity and sustained SD. Furth.rmore, we observed an unexpectedly prolonged survival in some patients, wh.ch.may indicate delayed effect of DC vaccination after completion of th. treatment. A prospective randomized ph.se-IIb or -III is needed to furth.r evaluate th. use of MelCancerVac? vaccine treatment in patients with.progressive NSCLC.

关键词： NSCLC Dendritic Cells Vaccination Tumor Lysate

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<i>In vitro</i>activity and function of B7-h.-Ig fusion protein

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Open Journal of Immunology 2013年第1期3卷 24-32页

作者： Susanne B. Rasmussen Mich.el Kosicki Signe G. Svendsen mogens h. claesson Nanna N. Kristensen Laboratory of Experimental Immunology Department of International Health Immunology and Microbiology The Faculty of Health Sciences University of Copenhagen Copenhagen Denmark

B7-h. h.s been sh.wn to inh.bit T cell proliferation, cytokine production and cell cycle in vitro. B7-h. deficient mice develop exacerbated disease in th. mouse models of Rh.umatoid Arth.itis (RA), Type 1 Diabetes (T1D) and Experimental Autoimmune Enceph.lomyelitis (EAE). On th. oth.r h.nd, B7-h.-Ig fusion protein h.s been documented to assuage th. symptoms in mouse models of RA, T1D, and multiple sclerosis in vivo. In th. present study, B7-h.-Ig bound to th. majority of h.man periph.ral blood monocytes and NK cells, but not to eith.r normal or activated T cells. B7-h.-Ig fusion protein was assayed for its effects in allogeneic mixed lymph.cyte culture (MLC) systems. Soluble B7- h.-Ig h.d no significant effect in th. MLC, but with.a tendency to promote allogeneic response. Immobilized, but not soluble B7-h.-Ig inh.bited plastic bound anti-CD3 mediated activation of T cells. Th.s inh.bition h.wever was largely due to B7-h.-Ig mediated displacement of anti-CD3 antibody from th. plastic plate. Finally, B7-h.-Ig h.d no effect on th. cytotoxicity mediated by NK and LAK cells in PBMC. Our findings th.s caution against th. interpretation of suppressive effect observed solely in plate-bound anti-CD3 mediated T cell co-stimulation in vitro.

关键词： CD28 Family B7-h. Fusion Protein MLC

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