Feldhaus A L, Evans L, Sutherland R A, Jones L A
Department of Molecular Biology, Targeted Genetics Corporation, Seattle, WA 98101, USA.
Gene Ther. 1997 Aug;4(8):833-8. doi: 10.1038/sj.gt.3300456.
We are evaluating strategies to enhance the in vivo proliferation and function of adoptively transferred antigen-specific T cells. Although the CD28 costimulatory pathway is important for T cell activation and proliferation, the expression of the ligands for CD28 is highly restricted. We have generated a chimeric receptor composed of the signaling domains of CD28 and the extracellular domain of CD2 which binds the widely expressed ligand CD58. The CD2/CD28 chimeric receptor was introduced into CTLL.2 cells via retrovirus infection and was shown to be expressed on the cell surface. By monitoring early and late components of the CD28 signaling pathway, the chimeric receptor was demonstrated to trigger the CD28 pathway in response to CD2 cross-linking. The possible utility of the CD2/CD28 chimeric receptor for adoptive immunotherapy is discussed.
我们正在评估增强过继转移的抗原特异性T细胞在体内增殖和功能的策略。虽然CD28共刺激途径对T细胞活化和增殖很重要，但CD28配体的表达受到高度限制。我们构建了一种嵌合受体，其由CD28的信号结构域和与广泛表达的配体CD58结合的CD2的胞外结构域组成。通过逆转录病毒感染将CD2/CD28嵌合受体导入CTLL.2细胞，并显示其在细胞表面表达。通过监测CD28信号通路的早期和晚期成分，证明嵌合受体在CD2交联时可触发CD28途径。本文讨论了CD2/CD28嵌合受体在过继免疫治疗中的潜在应用。
