PRODUCTION OF FUNCTIONAL CHIMAERIC MOUSE HUMAN-ANTIBODY
PRODUCTION OF FUNCTIONAL CHIMAERIC MOUSE HUMAN-ANTIBODY
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DOI：
10.1038/312643a0
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发表时间：
1984-01-01
期刊：
影响因子：
64.8
通讯作者：
SHULMAN, MJ
中科院分区：
文献类型：
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作者：
BOULIANNE, GL;HOZUMI, N;SHULMAN, MJ
单克隆抗体的可用性已经恢复了对免疫疗法的兴趣。通过施用适当特异性的免疫球蛋白来影响个体的免疫状态的能力可以提供疾病控制和预防的有力方法。与其他物种的免疫球蛋白相比，人免疫球蛋白（IG）可能是最好的治疗干预;它可能与受体的效应细胞更好地发挥作用，本身应该是免疫原性较低。小鼠杂交瘤系统的成功表明，实际上任何特异性的免疫球蛋白都可以从适当免疫的动物中获得。然而，在人类系统中，免疫方案受到伦理考虑的限制，并且尚不清楚是否可以从外源免疫的个体或从体外免疫的细胞获得具有所需特异性的人抗体产生细胞系。一种可能克服这些困难的方法是生产由小鼠可变区与人恒定区连接组成的抗体。因此，我们构建了免疫球蛋白基因，其中编码小鼠半抗原三硝基苯基（TNP）特异性可变区的DNA片段连接到编码人μ和κ恒定区的片段。这些“嵌合”基因表达为功能性TNP结合嵌合IgM。我们在这里报告这种新型IgM的一些特性。
The availability of monoclonal antibodies has revived interest in immunotherapy. The ability to influence an individual's immune state by administering immunoglobulin of the appropriate specificity may provide a powerful approach to disease control and prevention. Compared with immunoglobulin from other species, human immunoglobulin (Ig) might be best for such therapeutic intervention; it might function better with the recipient's effector cells and should itself be less immunogenic. The success of the mouse hybridoma system suggests that immunoglobulin of virtually any specificity can be obtained from a properly immunized animal. In the human system, however, immunization protocols are restricted by ethical considerations, and it is not yet clear whether human antibody-producing cell lines of the required specificity can be obtained from adventitiously immunized individuals or fromin vitroimmunized cells. A method which might circumvent these difficulties is to produce antibodies consisting of mouse variable regions joined to human constant regions. Therefore, we have constructed immunoglobulin genes in which the DNA segments encoding mouse variable regions specific for the hapten trinitrophenyl (TNP) are joined to segments encoding humanμandκconstant regions. These ‘chimaeric’ genes are expressed as functional TNP-binding chimaeric IgM. We report here some of the properties of this novel IgM.