A phase II randomized study of HIV-specific T-cell gene therapy in subjects with undetectable plasma viremia on combination antiretroviral therapy
A phase II randomized study of HIV-specific T-cell gene therapy in subjects with undetectable plasma viremia on combination antiretroviral therapy
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DOI：
10.1006/mthe.2002.0611
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发表时间：
2002-06-01
影响因子：
12.4
通讯作者：
Hege, KM
中科院分区：
文献类型：
--
作者：
Deeks, SG;Wagner, B;Hege, KM
高效抗逆转录病毒疗法（HAART）可以将HIV复制抑制到血浆中检测不到的水平，但不太可能根除病毒的细胞储存库。溶细胞的免疫疗法可能是靶向HIV复制的药物疗法的有用替代品。我们已经产生了HIV特异性CD4（+）和CD8（+）T细胞，其携带嵌合T细胞受体（CD4zeta），该嵌合T细胞受体由人CD4的细胞外和跨膜结构域（其结合HIVgp120）连接到CD3 T细胞受体的细胞内zeta信号链组成。CD4zeta修饰的T细胞可以抑制病毒复制，在体外杀死HIV感染的细胞，并在体内长时间存活。我们报告了一项II期随机试验的结果，该试验在40名接受HAART治疗的HIV感染者中比较了CD4zeta基因修饰的T细胞与未修饰的T细胞，
Highly active antiretroviral therapy (HAART) can suppress HIV replication to undetectable levels in plasma, but it is unlikely to eradicate cellular reservoirs of virus. Immunotherapies that are cytolytic may be useful adjuncts to drug therapies that target HIV replication. We have generated HIV-specific CD4(+) and CD8(+) T cells bearing a chimeric T-cell receptor (CD4zeta) composed of the extracellular and transmembrane domain of human CD4 (which binds HIVgp120) linked to the intracellular-zeta signaling chain of the CD3 T-cell receptor. CD4zeta-modified T cells can inhibit viral replication, kill HIV-infected cells in vitro, and survive for prolonged periods in vivo. We report the results of a phase II randomized trial of CD4zeta gene-modified versus unmodified T cells in 40 HIV-infected subjects on HAART with plasma viral loads