生物
细胞毒性T细胞
CD8型
免疫学
过继性细胞移植
细胞疗法
移植
T细胞
病毒学
造血
免疫系统
干细胞
体外
医学
细胞生物学
外科
生物化学
作者
Fabiana Rocha,Caio Raony Farina Silveira,Ancély Ferreira dos Santos,Ana Carolina Buzzo Stefanini,Nelson Hamerschlak,Luciana Cavalheiro Marti
标识
DOI:10.1016/j.cellimm.2023.104795
摘要
At present, recipients of allogeneic hematopoietic stem-cells are still suffering from recurrent infections after transplantation. Infusion of virus-specific T cells (VST) post-transplant reportedly fights several viruses without increasing the risk of de novo graft-versus-host disease. This study targeted cytomegalovirus (CMV) for the development of an innovative approach for generating a very specific VST product following Good Manufacturing Practices (GMP) guidelines. We used a sterile disposable compartment named the Leukoreduction System Chamber (LRS-chamber) from the apheresis platelet donation kit as the starting material, which has demonstrated high levels of T cells. Using a combination of IL-2 and IL-7 we could improve expansion of CMV-specific T cells. Moreover, by developing and establishing a new product protocol, we were able to stimulate VST proliferation and favors T cell effector memory profile. The expanded VST were enriched in a closed automated system, creating a highly pure anti-CMV product, which was pre-clinically tested for specificity in vitro and for persistence, biodistribution, and toxicity in vivo using NOD scid mice. Our results demonstrated very specific VST, able to secrete high amounts of interferon only in the presence of cells infected by the human CMV strain (AD169), and innocuous to cells partially HLA compatible without viral infection.
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