【摘 要】
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The efficacy and toxicity ofa lysate-pulsed autologous dendritic cell (DC)-based vaccine were evaluated in patients with advanced colorectal cancer (CRC).DCs were cultured from peripheral blood mononu
【机 构】
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Department of International Health Immunology and Microbiology Faculty of Health Sciences University
【出 处】
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BIT‘s2nd Annual World Cancer Congess-2009 (2009第二届癌症大会)
论文部分内容阅读
The efficacy and toxicity ofa lysate-pulsed autologous dendritic cell (DC)-based vaccine were evaluated in patients with advanced colorectal cancer (CRC).DCs were cultured from peripheral blood mononuclear cells in the presence of IL-4 and GM-CSF, then pulsed with an allogeneic tumor cell lysate (MelCancerVac,DanDrit Biotech, Copenhagen, Denmark) expressing high levels of MAGE-A antigens and further matured by a cytokine cocktail.Each patient received up to 10 intradermal vaccinations (3-5 × 106 cells/dose) at biweekly intervals.Prior to vaccination, patients were selected for presence of MAGE in tumor metastases.The most common MAGE-A gene expressed was MAGE-A4 (69.2%).Twenty patients recived a total of 161 vaccinations.Treatment was well-tolerated with minimal adverse events and quality of life measurements did not vary much across time.One patient experienced a partial response (5%; 95% CI, 1-24%) and seven patients achieved stable disease (35%; 95% CI, 18-57%) yielding a clinical benefit rate of 40% (95% CI, 22-61%).Although overall median progression free survival (PFS) was only 2.4 months (95% CI, 1.9-4.1 mths), five patients (20%) experience a prolonged progression free survival of more than 6 months with two patients being progression-free for more than 33 months.Overall, DC vaccination was associated with an increased DTH response towards the vaccine and a decline of regulatory T cells in peripheral blood.Using an antibody array-based detection system, we identified plasma proteins associated with tumor promotion, angiogenesis and cell migration which were significantly lowered in responding patients and therefore may correlate with vaccine efficacy and report a protein signature pre-vaccination distinguishing responders from non-responders.Conclusion: This phase Ⅱ vaccine study using consistently mature, allogenic tumor-lysate pulsed DCs has shown promising results and warrants further evaluation in a prospective randomized setting.
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