Volume 8 Issue 7
Jul.  2017
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Xiaojun Liu, Shuguang Jiang, Chongyun Fang, Hua Li, Xuhua Zhang, Fuqin Zhang, Carl H. June, Yangbing Zhao. Novel T cells with improved in vivo anti-tumor activity generated by RNA electroporation[J]. Protein&Cell, 2017, 8(7): 514-526. doi: 10.1007/s13238-017-0422-6
Citation: Xiaojun Liu, Shuguang Jiang, Chongyun Fang, Hua Li, Xuhua Zhang, Fuqin Zhang, Carl H. June, Yangbing Zhao. Novel T cells with improved in vivo anti-tumor activity generated by RNA electroporation[J]. Protein&Cell, 2017, 8(7): 514-526. doi: 10.1007/s13238-017-0422-6

Novel T cells with improved in vivo anti-tumor activity generated by RNA electroporation

doi: 10.1007/s13238-017-0422-6
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This study was supported by research grant R01CA120409 (CHJ, YZ) and a research grant from Tmunity Therapeutics Inc. (YZ).

  • Received Date: 2017-02-16
  • Rev Recd Date: 2017-04-20
  • The generation of T cells with maximal anti-tumor activities will significantly impact the field of T-cellbased adoptive immunotherapy. In this report, we found that OKT3/IL-2-stimulated T cells were phenotypically more heterogeneous, with enhanced anti-tumor activity in vitro and when locally administered in a solid tumor mouse model. To further improve the OKT3/IL-2-based T cell manufacturing procedure, we developed a novel T cell stimulation and expansion method in which peripheral blood mononuclear cells were electroporated with mRNA encoding a chimeric membrane protein consisting of a single-chain variable fragment against CD3 and the intracellular domains of CD28 and 4-1BB (OKT3-28BB). The expanded T cells were phenotypically and functionally similar to T cells expanded by OKT3/IL-2. Moreover, co-electroporation of CD86 and 4-1BBL could further change the phenotype and enhance the in vivo anti-tumor activity. Although T cells expanded by the coelectroporation of OKT3-28BB with CD86 and 4-1BBL showed an increased central memory phenotype, the T cells still maintained tumor lytic activities as potent as those of OKT3/IL-2 or OKT3-28BB-stimulated T cells. In different tumor mouse models, T cells expanded by OKT3-28BB RNA electroporation showed anti-tumor activities superior to those of OKT3/IL-2 T cells. Hence, T cells with both a less differentiated phenotype and potent tumor killing ability can be generated by RNA electroporation, and this T cell manufacturing procedure can be further optimized by simply co-delivering other splices of RNA, thus providing a simple and cost-effective method for generating high-quality T cells for adoptive immunotherapy.
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