Matejková E, Ocadlíková D, Smejkalová J, Muzíkova J, Raida L, Tousovská K, Pacasová R, Nenicková M, Tesarová E, Sterba J, Indrák K, Michálek J
Univerzitní Centrum Bunecné Imunoterapie, Masarykova Univerzita, Brno.
Klin Onkol. 2008;21(3):104-9.
Graft-versus-host disease (GVHD) is a severe complication of allogeneic transplantation of hematopoietic stem cells. Donor T cells play a major role in GVHD leading to the host tissue damage, mainly the skin, liver, and gastrointestinal tract. A selective depletion using an anti-CD25 immunotoxin can eliminate harmful alloreactive T cells while preserving other donor T cells with antileukemic and antiinfectious reactivity.
We performed 15 mixed lymphocyte reactions with clinical specimens from 12 patients with various types of leukemia (7x AML, 3x ALL, 1x CML, 1x CLL) and PBMC from 15 healthy volunteers from Transfusive station FN Brno Bohunice.
In our experiments we have demonstrated, that antileukemic (GVL) effect of donor, especially CD4+ T cells was well preserved (7.46%), while unfavourable alloreactive (GVH) reaction of donor T cells was completely removed. The graft-versus-host (GVH) reactivation of donor cells was negligible ever after repeated stimulation with irradiated patient's PBMC.
We have shown that anti-CD25 immunotoxin (IT), RFT5-SMPT-dgA, launched against alpha chain for human interleukin 2 (IL-2), led to long-term selective depletion of alloreactive donor T cell clones while their antileukemic activity was well preserved. Base on our results the clinical phase I/II study was designed. This study was initiated in year 2007 in three clinical centers in Czech Republic.
移植物抗宿主病（GVHD）是异基因造血干细胞移植的一种严重并发症。供体T细胞在GVHD中起主要作用，导致宿主组织损伤，主要是皮肤、肝脏和胃肠道。使用抗CD25免疫毒素进行选择性清除可消除有害的同种异体反应性T细胞，同时保留具有抗白血病和抗感染反应性的其他供体T细胞。
我们用来自12例不同类型白血病患者（7例急性髓系白血病、3例急性淋巴细胞白血病、1例慢性髓系白血病、1例慢性淋巴细胞白血病）的临床标本以及来自布尔诺博胡尼采输血站的15名健康志愿者的外周血单核细胞进行了15次混合淋巴细胞反应。
在我们的实验中，我们证明供体的抗白血病（GVL）效应，尤其是CD4 + T细胞的效应得到了很好的保留（7.46%），而供体T细胞不利的同种异体反应性（GVH）反应被完全消除。即使在用辐照后的患者外周血单核细胞反复刺激后，供体细胞的移植物抗宿主（GVH）再激活也可忽略不计。
我们已经表明，针对人白细胞介素2（IL - 2）α链的抗CD25免疫毒素（IT）RFT5 - SMPT - dgA可导致同种异体反应性供体T细胞克隆的长期选择性清除，同时其抗白血病活性得到很好的保留。基于我们的结果设计了临床I/II期研究。该研究于2007年在捷克共和国的三个临床中心启动。
