Simple and Efficient Generation of Virus-specific T Cells for Adoptive Therapy Using Anti-4-1BB Antibody
Simple and Efficient Generation of Virus-specific T Cells for Adoptive Therapy Using Anti-4-1BB Antibody
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使用抗 4-1BB 抗体简单高效地生成用于过继治疗的病毒特异性 T 细胞
DOI：
10.1097/cji.0000000000000069
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
and Makoto Murata
中科院分区：
文献类型：
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作者：
Nobuhiko Imahashi;Tetsuya Nishida;Tatsunori Goto;Seitaro Terakura;Keisuke Watanabe;Ryo Hanajiri;Reona Sakemura;Misa Imai;Hitoshi Kiyoi;Tomoki Naoe;and Makoto Murata
虽然最近的研究病毒特异性T细胞（VST）治疗异基因造血干细胞移植后的病毒感染已经显示出有希望的结果，需要简单和更少的时间密集型和劳动密集型的方法来产生VST的VST治疗的更广泛的应用。我们研究了抗CD 28和抗4-1BB抗体在产生VST中的功效，这些抗体可以为T细胞提供与抗原呈递细胞强度相似的共刺激信号。当用病毒肽与同种型对照、抗CD 28或抗4-1BB抗体一起刺激外周血单核细胞时，抗4-1BB抗体产生最高数量的VST，其平均是用同种型对照抗体产生的VST的7.9倍。与单独抗4-1BB抗体相比，抗CD 28和抗4- 1BB抗体的组合未导致VST数量增加。重要的是，无论VST的表位如何，都观察到抗4-1BB抗体的积极作用。相反，树突状细胞（DC）产生VST的能力根据VST的表位有很大不同。此外，用DC产生的VST的数量至多与用抗4-1BB抗体产生的VST的数量相似。与用对照抗体或DC产生的VST相比，用抗4-1BB抗体产生的VST没有导致所产生的VST的过度分化或功能恶化。总之，VST可以通过简单地用病毒肽和抗4-1BB抗体刺激外周血单个核细胞而快速有效地产生，而不使用抗原呈递细胞。我们建议使用抗4-1BB抗体作为一种新的策略，以产生VST过继治疗。
Although recent studies of virus-specific T-cell (VST) therapy for viral infections after allogeneic hematopoietic stem cell transplantation have shown promising results, simple and less time-intensive and labor-intensive methods are required to generate VSTs for the wider application of VST therapy. We investigated the efficacy of anti-CD28 and anti-4-1BB antibodies, which can provide T cells with costimulatory signals similar in strength to those of antigen-presenting cells, in generating VSTs. When peripheral blood mononuclear cells were stimulated with viral peptides together with isotype control, anti-CD28, or anti-4-1BB antibodies, anti-4-1BB antibodies yielded the highest numbers of VSTs, which were on an average 7.9 times higher than those generated with isotype control antibody. The combination of anti-CD28 and anti-4-1BB antibodies did not result in increased numbers of VSTs compared with anti-4-1BB antibody alone. Importantly, the positive effect of anti-4-1BB antibody was observed regardless of the epitopes of the VSTs. In contrast, the capacity of dendritic cells (DCs) to generate VSTs differed considerably depending on the epitopes of the VSTs. Furthermore, the numbers of VSTs generated with DCs were at most similar to those generated with the anti-4-1BB antibody. Generation of VSTs with anti-4-1BB antibody did not result in excessive differentiation or deteriorated function of the generated VSTs compared with those generated with control antibody or DCs. In conclusion, VSTs can be generated rapidly and efficiently by simply stimulating peripheral blood mononuclear cells with viral peptide and anti-4-1BB antibody without using antigen-presenting cells. We propose using anti-4-1BB antibody as a novel strategy to generate VSTs for adoptive therapy.