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

Protein & Cell
Xiaojun LiuYangbing Zhao

Abstract

The generation of T cells with maximal anti-tumor activities will significantly impact the field of T-cell-based 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 co-electroporation 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 e...Continue Reading

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Citations

Jun 3, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Dapeng ZhouTorsten Tonn
Oct 20, 2018·Cellular and Molecular Life Sciences : CMLS·Thomas SchlakeIngo Jordan
Apr 5, 2020·Journal of Hematology & Oncology·Chongxian PanLei Zheng
Aug 16, 2021·Blood Cancer Journal·Alejandra LeivasJoaquín Martínez-López

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Datasets Mentioned

BETA
US7575923

Methods Mentioned

BETA
xenograft
Flow cytometry
ELISA
in vitro transcription
bioluminescence imaging

Software Mentioned

STATA
Prism
Living Image

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