The immune modulator capacity of antigen-pulsed dendritic cells (DC) has been documented in patients with cancers and in animal models of chronic viral infections. Cancer antigen-pulsed DC are now used for treating patients with cancer. But viral antigen-pulsed DC are not used in chronic viral-infected patients because safety of antigen-pulsed DC has not been evaluated in these patients. DC were isolated from human peripheral blood mononuclear cells by culturing with human-grade granulocyte-macrophage colony stimulating factor and interleukin-4. Human blood DC were cultured with hepatitis B surface antigen (HBsAg) for 8h to prepare HBsAg-pulsed DC. After immunogenicity assessment of HBsAg-pulsed DC in vitro, five million HBsAg-pulsed DC were administered intradermally to five patients with chronic hepatitis B (CHB) 1-3 times. HBsAg-pulsed DC were immunogenic in nature because they produced significantly higher levels of interleukin-12 and interferon-γ compared to unpulsed DC (P<0.05). Also, HBsAg-pulsed DC induced proliferation of HBsAg-specific T lymphocytes in vitro. CHB patients injected with HBsAg-pulsed DC did not exhibit generalized inflammation, exacerbation of liver damage, abnormal kidney function, or features of autoimmunity. Administration of HBsAg-pulsed DC induced anti-HBs in two patients and HBsAg-specific cellular immunity in 1 patient. This is the first study about preparation of antigen-pulsed DC using human consumable materials for treating patients with CHB. Because HBsAg-pulsed DC were safe for all patients with CHB and had immune modulation capacity in some patients, phase I and phase II clinical trials with antigen-pulsed DC in CHB and other chronic infections are warranted.

译文

:已在癌症患者和慢性病毒感染的动物模型中记录了抗原脉冲树突状细胞(DC)的免疫调节剂能力。癌症抗原脉冲DC现在用于治疗癌症患者。但是在慢性病毒感染的患者中不使用病毒抗原脉冲DC,因为尚未评估这些患者中抗原脉冲DC的安全性。通过与人级粒细胞-巨噬细胞集落刺激因子和白介素-4培养,从人外周血单核细胞中分离DC。将人血DC与乙型肝炎表面抗原(HBsAg)培养8小时,以制备HBsAg脉冲DC。在对HBsAg脉冲DC进行了体外免疫原性评估后,对5例慢性乙型肝炎(CHB)患者进行了5百万次HBsAg脉冲DC皮内给药。 HBsAg脉冲的DC具有免疫原性,因为与无脉冲的DC相比,它们产生的白细胞介素12和干扰素-γ水平明显更高(P <0.05)。同样,HBsAg脉冲的DC诱导了HBsAg特异性T淋巴细胞的体外增殖。注射HBsAg脉冲DC的CHB患者未表现出全身性炎症,肝损害加剧,肾功能异常或自身免疫特征。两名患者接受HBsAg脉冲直流诱导的抗HBs治疗,另一名患者接受HBsAg特异性细胞免疫。这是有关使用人类可消耗材料治疗CHB患者制备抗原脉冲DC的第一项研究。因为HBsAg脉冲DC对所有CHB患者都是安全的,并且对某些患者具有免疫调节能力,所以有必要在抗原性DC在CHB和其他慢性感染中进行I期和II期临床试验。

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