Hege K M, Cooke K S, Finer M H, Zsebo K M, Roberts M R
Department of Immunology and Cell Biology, Cell Genesys Inc., Foster City, California 94404, USA.
J Exp Med. 1996 Dec 1;184(6):2261-9. doi: 10.1084/jem.184.6.2261.
Gene modification of hematopoietic stem cells (HSC) with antigen-specific, chimeric, or "universal" immune receptors (URs) is a novel but untested form of targeted immunotherapy. A human immunodeficiency virus (HIV) envelope-specific UR consisting of the extracellular domain of human CD4 linked to the zeta chain of the T cell receptor (CD4 zeta) was introduced ex vivo into murine HSC by retroviral transduction. After transplantation into immunodeficient SCID mice, sustained high level expression of CD4 zeta was observed in circulating myeloid and natural killer cells. CD4 zeta-transplanted mice were protected from challenge with a lethal dose of a disseminated human leukemia expressing HIV envelope. These results demonstrate the ability of chimeric receptors bearing zeta-signaling domains to activate non-T cell effector populations in vivo and thereby mediate systemic immunity.
用抗原特异性、嵌合或“通用”免疫受体（UR）对造血干细胞（HSC）进行基因改造是一种新型的但未经测试的靶向免疫疗法形式。一种由与T细胞受体的ζ链（CD4ζ）相连的人CD4细胞外结构域组成的人免疫缺陷病毒（HIV）包膜特异性UR，通过逆转录病毒转导在体外导入小鼠造血干细胞。移植到免疫缺陷的SCID小鼠体内后，在循环髓系细胞和自然杀伤细胞中观察到CD4ζ的持续高水平表达。移植了CD4ζ的小鼠受到致死剂量的表达HIV包膜的播散性人类白血病攻击时受到保护。这些结果证明了带有ζ信号结构域的嵌合受体在体内激活非T细胞效应群体并由此介导全身免疫的能力。
