4.5 Article

Optimizing adoptive polyclonal T cell immunotherapy of lymphomas, using a chimeric T cell receptor possessing CD28 and CD137 costimulatory domains

期刊

HUMAN GENE THERAPY
卷 18, 期 8, 页码 712-725

出版社

MARY ANN LIEBERT INC
DOI: 10.1089/hum.2007.028

关键词

-

资金

  1. NCI NIH HHS [R01 CA92302, R21 CA 117131-01A] Funding Source: Medline
  2. NCRR NIH HHS [M01-RR-00037] Funding Source: Medline

向作者/读者索取更多资源

We previously demonstrated the feasibility of generating therapeutic numbers of cytotoxic T lymphocyte ( CTL) clones expressing a CD20-specific scFvFc: CD3 zeta chimeric T cell receptor ( cTCR), making them specifically cytotoxic for CD20(+) B lymphoma cells. However, the process of generating and expanding the CTL clones was laborious, the CTL clones expressed the cTCR at low surface density, and they exhibited suboptimal proliferation and cytotoxicity. To improve the performance of the CTLs in vitro and in vivo, we engineered second-generation plasmid constructs containing a translational enhancer ( SP163) and CD28 and CD137 costimulatory domains in cis with the CD3 zeta intracellular signaling domain of the cTCR gene. Furthermore, we verified the superiority of generating genetically modified polyclonal T cells expressing the second-generation cTCR rather than T cell clones. Our results demonstrate that SP163 enhances the surface expression of the cTCR; that the second-generation cTCR improves CTL activation, proliferation, and cytotoxicity; and that polyclonal T cells proliferate rapidly in vitro and mediate potent CD20-specific cytotoxicity. This study provides the preclinical basis for a clinical trial of adoptive T cell immunotherapy for patients with relapsed CD20(+) mantle cell lymphoma and indolent lymphomas.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.5
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据