人工抗原提呈细胞大规模体外扩增γδ T细胞

IF 3.2 4区 医学 Q3 IMMUNOLOGY
Justin C Boucher, Bin Yu, Gongbo Li, Bishwas Shrestha, David Sallman, Ana Marie Landin, Cheryl Cox, Kumar Karyampudi, Claudio Anasetti, Marco L Davila, Nelli Bejanyan
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引用次数: 5

摘要

恶性肿瘤患者较高的γδ T细胞计数与较好的生存率相关。然而,γδ T细胞在血液中很少见,在恶性肿瘤患者中功能受损。唑来膦酸(zol)和白细胞介素-2 (IL-2)在体内扩增自体γδ T细胞治疗多种恶性肿瘤的研究取得了可喜的结果。在这里,我们证明了zol和IL-2,结合一种新的基因工程K-562 CD3scFv/CD137L/CD28scFv/IL15RA四联体人工抗原呈递细胞(aAPC),使用符合良好生产规范(GMP)的方案,有效地扩增异体供体来源的γδ T细胞,足以达到将来临床使用的细胞剂量。在与aAPC共培养第10天后,我们获得了633倍的γδ T细胞扩增,表现出中心(47%)和效应(43%)记忆表型。此外,>90%的扩增的γδ T细胞表达NKG2D,尽管它们的细胞表面表达PD1和LAG3抑制检查点受体较低。体外实时细胞毒性分析表明,扩增的γδ T细胞能有效杀伤靶细胞。我们的研究结果表明,使用四联体aAPC和zol/IL-2可以在gmp样环境中实现供体来源的γδ T细胞的大规模体外扩增,用于临床应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Large Scale Ex Vivo Expansion of γδ T cells Using Artificial Antigen-presenting Cells.

Large Scale Ex Vivo Expansion of γδ T cells Using Artificial Antigen-presenting Cells.

Large Scale Ex Vivo Expansion of γδ T cells Using Artificial Antigen-presenting Cells.

Large Scale Ex Vivo Expansion of γδ T cells Using Artificial Antigen-presenting Cells.

Higher γδ T cell counts in patients with malignancies are associated with better survival. However, γδ T cells are rare in the blood and functionally impaired in patients with malignancies. Promising results are reported on the treatment of various malignancies with in vivo expansion of autologous γδ T cells using zoledronic acid (zol) and interleukin-2 (IL-2). Here we demonstrated that zol and IL-2, in combination with a novel genetically engineered K-562 CD3scFv/CD137L/CD28scFv/IL15RA quadruplet artificial antigen-presenting cell (aAPC), efficiently expand allogeneic donor-derived γδ T cells using a Good Manufacturing Practice (GMP) compliant protocol sufficient to achieve cell doses for future clinical use. We achieved a 633-fold expansion of γδ T cells after day 10 of coculture with aAPC, which exhibited central (47%) and effector (43%) memory phenotypes. In addition, >90% of the expanded γδ T cells expressed NKG2D, although they have low cell surface expression of PD1 and LAG3 inhibitory checkpoint receptors. In vitro real-time cytotoxicity analysis showed that expanded γδ T cells were effective in killing target cells. Our results demonstrate that large-scale ex vivo expansion of donor-derived γδ T cells in a GMP-like setting can be achieved with the use of quadruplet aAPC and zol/IL-2 for clinical application.

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来源期刊
Journal of Immunotherapy
Journal of Immunotherapy 医学-免疫学
CiteScore
6.90
自引率
0.00%
发文量
79
审稿时长
6-12 weeks
期刊介绍: Journal of Immunotherapy features rapid publication of articles on immunomodulators, lymphokines, antibodies, cells, and cell products in cancer biology and therapy. Laboratory and preclinical studies, as well as investigative clinical reports, are presented. The journal emphasizes basic mechanisms and methods for the rapid transfer of technology from the laboratory to the clinic. JIT contains full-length articles, review articles, and short communications.
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