Department of Medical Sciences, Toshiba General Hospital, Tokyo, Japan.
J Viral Hepat. 2011 Jun;18(6):408-14. doi: 10.1111/j.1365-2893.2010.01320.x.
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.
已在癌症患者和慢性病毒感染动物模型中证实了抗原脉冲树突状细胞（DC）的免疫调节能力。现在，癌症抗原脉冲 DC 被用于治疗癌症患者。但是，尚未在慢性病毒感染患者中使用病毒抗原脉冲 DC，因为尚未在这些患者中评估抗原脉冲 DC 的安全性。通过用人粒细胞-巨噬细胞集落刺激因子和白细胞介素-4 培养从人外周血单核细胞中分离 DC。用人乙型肝炎表面抗原（HBsAg）培养人血 DC 8 小时，制备 HBsAg 脉冲 DC。在体外评估 HBsAg 脉冲 DC 的免疫原性后，将 500 万个 HBsAg 脉冲 DC 皮内注射到 5 名慢性乙型肝炎（CHB）患者中，1-3 次。HBsAg 脉冲 DC 具有免疫原性，因为与未脉冲 DC 相比，其产生的白细胞介素-12 和干扰素-γ水平明显更高（P<0.05）。此外，HBsAg 脉冲 DC 诱导 HBsAg 特异性 T 淋巴细胞在体外增殖。接受 HBsAg 脉冲 DC 注射的 CHB 患者未表现出全身炎症、肝损伤加重、肾功能异常或自身免疫特征。在两名患者中诱导了抗-HBs 的产生，在 1 名患者中诱导了 HBsAg 特异性细胞免疫。这是第一项使用人可消耗材料制备抗原脉冲 DC 以治疗 CHB 患者的研究。由于 HBsAg 脉冲 DC 对所有 CHB 患者均安全且在某些患者中具有免疫调节能力，因此有必要进行 HBsAg 脉冲 DC 在 CHB 和其他慢性感染中的 I 期和 II 期临床试验。
