Safety and immunogenicity of hepatitis B surface antigen-pulsed dendritic cells

StephenW

Viral Hepat. 2010 May 17. [Epub ahead of print]

Safety and immunogenicity of hepatitis B surface antigen-pulsed dendritic
cells in patients with chronic hepatitis B.

Akbar SM, Furukawa S, Horiike N, Abe M, Hiasa Y, Onji M.

Department of Medical Sciences, Toshiba General Hospital, Tokyo, Japan.


Abstract

Summary. 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 8 h 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-gamma 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.

PMID: 20487261 [PubMed - as supplied by publisher]



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　　安全及免疫原性的乙肝表面负载树突细胞
　　病毒性Hepat 2010年5月17号。出版前Epub。)
　　
　　安全及免疫原性的乙肝表面负载树突
　　细胞的慢性乙肝患者当中。
　　
　　Furukawa阿克巴钐、硫、Horiike N,安倍,Hiasa Y,Onji米。
　　
　　医学科学部门,东芝总医院,日本东京。
　　
　　
　　摘要
　　
　　总结。免疫调节的负载能力(DC)的树突细胞,
　　被记录在癌症患者在动物模型,对慢性
　　滤过性病毒感染。现在使用直流负载癌症治疗的病人
　　死于癌症。但是病毒不使用直流负载在慢性
　　viral-infected病人因为安全的直流负载尚未
　　这些病人的评估。直流电是孤立的,从人类的周边血液
　　单核细胞通过培养和human-grade granulocyte-macrophage殖民地
　　刺激因子和interleukin-4。人类的血液培养与直流
　　乙肝表面抗原(HBsAg)8小时准备HBsAg-pulsed直流。之后,
　　免疫原性评价的HBsAg-pulsed直流体外,500万
　　HBsAg-pulsed直流都intradermally 5例慢性
　　乙肝1-3倍。本质上是immunogenic HBsAg-pulsed DC
　　因为他们产生显著的高水平的interleukin-12和
　　相比unpulsed间直流(P < 0.05)。同样,HBsAg-pulsed直流
　　HBsAg-specific T淋巴细胞增殖的诱导体外。慢乙肝患者
　　注射HBsAg-pulsed直流,并没有显示出广义发炎,
　　肝损伤的加重,异常的肾脏功能,或特征
　　自体免疫疾病。HBsAg-pulsed直流诱导anti-HBs管理两个
　　病人和HBsAg-specific细胞免疫,1例病人。这是第一次
　　研究了利用人类制备负载消耗品材料的直流
　　治疗,但很少有抗病毒能力。因为HBsAg-pulsed直流是安全的
　　有,但很少有抗病毒能力和免疫调节能力在某些病人来说,第一阶段
　　第二阶段的临床试验,以直流负载在慢乙肝和其他慢性病
　　感染的保质期。
　　
　　PMID:20487261[公共医学-提供出版商]