Toward a Rapid Production of Multivirus-Specific T Cells Targeting BKV, Adenovirus, CMV, and EBV from Umbilical Cord Blood

被引:34
作者
Dave, Hema [1 ,2 ,3 ]
Luo, Min [1 ,3 ]
Blaney, J. W. [9 ,10 ]
Patel, Shabnum [1 ,3 ,8 ]
Barese, Cecilia [1 ,3 ]
Cruz, Conrad Russell [1 ,3 ,4 ,5 ]
Shpall, Elizabeth J. [11 ]
Bollard, Catherine M. [1 ,3 ,4 ,5 ,6 ,7 ,8 ]
Hanley, Patrick J. [1 ,3 ,4 ,5 ,7 ]
机构
[1] Childrens Natl Med Ctr, Ctr Canc & Immunol Res, Washington, DC 20010 USA
[2] Childrens Natl Med Ctr, Div Oncol, Washington, DC 20010 USA
[3] Childrens Natl Med Ctr, Program Cell Enhancement & Technol Immunotherapy, Washington, DC 20010 USA
[4] George Washington Univ, Sch Med, Washington, DC 20037 USA
[5] Childrens Natl Med Ctr, Sheikh Zayed Inst, Washington, DC 20010 USA
[6] Childrens Natl Med Ctr, Div Allergy & Immunol, Washington, DC 20010 USA
[7] Childrens Natl Med Ctr, Div Blood & Marrow Transplantat, Washington, DC 20010 USA
[8] George Washington Univ, Inst Biomed Sci, Washington, DC 20037 USA
[9] Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA
[10] Houston Methodist Hosp, Houston, TX 77030 USA
[11] MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA
来源
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT | 2017年 / 5卷
关键词
EPSTEIN-BARR-VIRUS; IMMUNE RECONSTITUTION; HEMORRHAGIC CYSTITIS; ACUTE-LEUKEMIA; BONE-MARROW; TRANSPLANTATION; LYMPHOCYTES; OUTCOMES; THERAPY; INFECTION;
D O I
10.1016/j.omtm.2017.02.001
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Umbilical cord blood (CB) has emerged as an effective alternative donor source for hematopoietic stem cell transplantation. Despite this success, the prolonged duration of immune suppression following CB transplantation and the naivete of CB T cells leave patients susceptible to viral infections. Adoptive transfer of ex vivo-expanded virus-specific T cells from CB is both feasible and safe. However, the manufacturing process of these cells is complicated, lengthy, and labor-intensive. We have now developed a simplified method to manufacture a single culture of polyclonal multivirus-specific cytotoxic T cells in less than 30 days. It eliminates the need for a live virus or transduction with a viral vector, thus making this approach widely available and GMP-applicable to target multiple viruses. The use of overlapping PepMixes as a source of antigen stimulation enable expansion of the repertoire of the T cell product to any virus of interest and make it available as a third party "off the shelf" treatment for viral infections following transplantation.
引用
收藏
页码:13 / 21
页数:9
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