加拿大新型艾滋病疗法首次临床试验获成功
2009-12-03 20:06:00   来源：丁香园   作者：  评论：0 点击：

据加拿大麦吉尔大学健康中心网站报道，该中心研究人员开发的新型艾滋病治疗方法首次临床试验获得成功。研究人员称，该疗法可能比目前流行的鸡尾酒疗法更有效，前景光明。

报道称，该疗法由麦吉尔大学健康中心研究所J-P·鲁迪博士和蒙特利尔大学R·赛卡莱博士共同开发，作为一种免疫疗法，其可针对不同病人量身定制，通过注射疫苗，“引导”免疫系统对抗艾滋病感染者体内的特定艾滋病病毒。在第一阶段临床试验中，研究人员将该疗法与抗逆转录病毒药物结合使用，效果良好，其结果公布在最近的《临床免疫学》（Clinical Immunology）杂志上。第二阶段临床试验目前正在加拿大8个不同地点进行，其主要目标是检测该疗法自身的有效性。

新疗法使用树突状细胞作为媒介，这些细胞取自艾滋病病毒感染者体内，后经体外培养。作为目前所知的功能最强的抗原递呈细胞，树突状细胞会递呈侵入的病毒物质，使人体的其余免疫系统能够对侵入的病毒进行识别和攻击。“它们是人体免疫反应的‘伟大的指挥官’”，鲁迪博士解释说，“有了它们，你就可以推动免疫系统，在同一时间内发挥其所有的功能”。临床试验中，树突状细胞暴露在特定病人的艾滋病病毒RNA之下，这种接触会使细胞发展其针对特定病毒株的防御力。经过修正的细胞，称为AGS-004，会被再次注射到病人体内。临床试验结果表明，AGS-004几乎没有副作用，同时患者体内的CD8-淋巴细胞含量也显著增加。CD8-淋巴细胞是人体免疫系统的“攻击”细胞。

报道称，鲁迪博士希望开发出一种新型艾滋病治疗方法，通过这种方式来刺激人体免疫系统对抗艾滋病病毒。比起抗逆转录病毒治疗，这种疗法需要的注射量更少，产生的毒性持续时间更短。研究人员相信，这种新疗法可能比目前流行的抗逆转录病毒“鸡尾酒”疗法更有效，具有巨大的发展空间。

Immunologic activity and safety of autologous HIV RNA-electroporated dendritic cells in HIV-1 infected patients receiving antiretroviral therapy

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Jean-Pierre Routya, b, , , Mohamed-Rachid Boulasselc, Bader Yassine-Diabb, d, e, Charles Nicolettef, Don Healeyf, Renu Jainf, Claire Landryd, e, Oleg Yegorovb, d, e, Irina Tcherepanovaf, Tamara Monesmithf, Lothar Finkef and Rafick-Pierre Sékalyb, d, e, ,

aImmunodeficiency Service and Division of Hematology, McGill University Health Centre, McGill University, Montreal, Qc, Canada

bInstitut national de la Santé et de la Recherche médicale U743, Centre de Recherche, Centre Hospitalier de l'Université de Montréal, Montreal, Qc, Canada

cDivision of Hematology, McGill University Health Centre, Montreal, Qc, Canada

dLaboratoire d'Immunologie, Centre de Recherche, Hôpital Saint-Luc, Centre Hospitalier de l'Université de Montréal, Montreal, Qc, Canada

eNational Immune Monitoring Laboratory, Montreal, Qc, Canada

fArgos Therapeutics, Inc, Durham, NC, USA

Received 8 June 2009; accepted 22 September 2009. Available online 4 November 2009.

Abstract
Immunogenicity, manufacturing feasibility, and safety of a novel, autologous dendritic cell (DC)-based immunotherapy (AGS-004) was evaluated in ten human immunodeficiency virus type 1 (HIV-1)-infected adults successfully treated with antiretroviral therapy (ART). Personalized AGS-004 was produced from autologous monocyte-derived DCs electroporated with RNA encoding CD40L and HIV antigens (Gag, Vpr, Rev, and Nef) derived from each subjects' pre-ART plasma. Patients received monthly injections of AGS-004 in combination with ART. AGS-004 was produced within a mean of 6 weeks and yielded 4-12 doses/subject Full or partial HIV-specific proliferative immune responses occurred in 7 of 9 evaluable subjects. Responses were specific for the AGS-004 presented HIV antigens and preferentially targeted CD8+ T cells. Mild adverse events included flu-like symptoms, fatigue, and injection site reactions. No evidence of autoimmunity, changes in viral load, or significant changes in absolute CD4+ and CD8+ T cell counts were observed. This pilot study supports the further clinical investigation of AGS-004.

Keywords: HIV; Immunotherapy; Vaccine; Dendritic cells; Acquired immunodeficiency syndrome