Use of an anti-pan T-lymphocyte ricin a chain immunotoxin in steroid-resistant acute graft-versus-host disease.
Use of an anti-pan T-lymphocyte ricin a chain immunotoxin in steroid-resistant acute graft-versus-host disease.
复制标题
抗泛T淋巴细胞蓖麻毒蛋白链免疫毒素在类固醇抗性急性移植物抗宿主病中的应用。
作者：
Byers Vs;PJ Henslee;N. Kernan;B. Blazar;R. Gingrich;G. Phillips;C. Lemaistre;G. Gilliland;J. Antin;P. Martin
同种异体骨髓移植后急性类固醇抵抗性移植物抗宿主病（AGVHD）通常是致命的。对于这种t淋巴细胞介导的疾病，一种新的治疗方法是使用一种免疫毒素H65-RTA，它由一种单克隆抗体组成，该抗体识别CD5淋巴细胞分化抗原偶联到蓖麻毒素A链，蓖麻毒素A链是一种抑制蛋白质合成的细胞毒性酶。在一项I-II期剂量递增研究中，这种淋巴细胞靶向免疫毒素在严重AGVHD患者中的安全性和有效性进行了评估，其中两个剂量为中间剂量，组扩大。34名患者每天接受多达14次的免疫毒素静脉输注。主要的副作用是体质症状，如疲劳和肌痛，在所有剂量下都可以看到体重增加的低白蛋白血症。对32例患者进行病情改善或缓解的评估。持久的完全或部分反应与剂量无关，在16例患者中可见。皮肤GVHD的反应发生率最高（73%），尽管胃肠道GVHD（45%）和肝脏GVHD（28%）也有改善或缓解。与无反应的患者相比，反应患者的生存期在任何时候都显着延长（P = .03）。治疗与外周血T淋巴细胞的快速下降有关，这种下降在治疗后持续超过1个月。23例患者中有6例出现抗免疫毒素抗体；这些抗体滴度低，不能阻断免疫毒素与T细胞的结合。本研究结果表明，抗t淋巴细胞免疫毒素可能形成一类新的免疫抑制剂，用于治疗t淋巴细胞介导的疾病。
Acute steroid-resistant graft-versus-host disease (AGVHD) after allogeneic bone marrow transplantation is frequently fatal. A new treatment for this T-lymphocyte-mediated condition uses an immunotoxin, H65-RTA, comprised of a monoclonal antibody that recognizes the CD5 lymphocyte differentiation antigen coupled to ricin A chain, a cytotoxic enzyme that inhibits protein synthesis. The safety and efficacy of this lymphocyte-targeted immunotoxin was evaluated in patients with severe AGVHD in a phase I-II dose escalation study with group expansion at the two middle doses. Thirty-four patients received up to 14 daily intravenous infusions of the immunotoxin. The principal side effects were constitutional symptoms such as fatigue and myalgias, and hypoalbuminemia with weight gain was seen at all doses. Thirty-two patients were evaluated for improvement or resolution of disease. Durable complete or partial responses were not dose-related and were seen in 16 patients. Skin GVHD had the highest incidence of response (73%), although improvement or resolution in gastrointestinal tract (45%) and liver (28%) GVHD was also noted. Survival in responding patients was significantly prolonged at all times as compared with those with no response (P = .03). Treatment was associated with a rapid decrease in peripheral blood T lymphocytes, which persisted for greater than 1 month after therapy. Anti-immunotoxin antibodies were seen in 6 of the 23 patients tested; these were of low titer and did not block immunotoxin binding to T cells. Results of this study indicate that anti-T-lymphocyte immunotoxins may form a new class of immunosuppressive agents useful in T-lymphocyte-mediated diseases.
鼠单克隆抗 T 细胞抗体，用于治疗类固醇耐药的急性移植物抗宿主病。
影响因子：
2.7
作者：
Remlinger,K;Martin,PJ;Hansen,JA;Doney,KC;Smith,A;Deeg,HJ;Sullivan,K;Storb,R;Thomas,ED
通讯作者：
Thomas,ED
用抗 CD3 单克隆抗体治疗急性移植物抗宿主病。
DOI：
10.1016/s0272-6386(88)80201-4
发表时间：
1988
期刊：
American journal of kidney diseases : the official journal of the National Kidney Foundation
影响因子：
--
作者：
Martin,PJ;Hansen,JA;Anasetti,C;Zutter,M;Durnam,D;Storb,R;Thomas,ED
通讯作者：
Thomas,ED