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嵌合抗原受体T细胞对白血病的持续缓解

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发表于 2015-12-2 17:48:03 | 显示全部楼层 |阅读模式
Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia
BACKGROUND
Relapsed acute lymphoblastic leukemia (ALL) is difficult to treat despite the availability of aggressive therapies. Chimeric antigen receptor–modified T cells targeting CD19 may overcome many limitations of conventional therapies and induce remission in patients with refractory disease.
METHODS
We infused autologous T cells transduced with a CD19-directed chimeric antigen
receptor (CTL019) lentiviral vector in patients with relapsed or refractory ALL at
doses of 0.76×106 to 20.6×106 CTL019 cells per kilogram of body weight. Patients
were monitored for a response, toxic effects, and the expansion and persistence of
circulating CTL019 T cells.
RESULTS
A total of 30 children and adults received CTL019. Complete remission was
achieved in 27 patients (90%), including 2 patients with blinatumomab-refractory
disease and 15 who had undergone stem-cell transplantation. CTL019 cells proliferated
in vivo and were detectable in the blood, bone marrow, and cerebrospinal
fluid of patients who had a response. Sustained remission was achieved with a
6-month event-free survival rate of 67% (95% confidence interval [CI], 51 to 88)
and an overall survival rate of 78% (95% CI, 65 to 95). At 6 months, the probability
that a patient would have persistence of CTL019 was 68% (95% CI, 50 to 92) and the probability that a patient would have relapse-free B-cell aplasia was 73%
(95% CI, 57 to 94). All the patients had the cytokine-release syndrome. Severe
cytokine-release syndrome, which developed in 27% of the patients, was associated
with a higher disease burden before infusion and was effectively treated with
the anti–interleukin-6 receptor antibody tocilizumab.
CONCLUSIONS
Chimeric antigen receptor–modified T-cell therapy against CD19 was effective in
treating relapsed and refractory ALL. CTL019 was associated with a high remission
rate, even among patients for whom stem-cell transplantation had failed, and
durable remissions up to 24 months were observed. (Funded by Novartis and others;
CART19 ClinicalTrials.gov numbers, NCT01626495 and NCT01029366.)
嵌合抗原受体T细胞对白血病的持续缓解
背景:
复发性急性淋巴细胞白血病(ALL)很难被治疗,虽然有一些攻击性的治疗方法可以使用。嵌合抗原受体修饰的T细胞能够靶向CD19,可能克服传统治疗的局限,并且缓解难治性病人的疾病。
方法:
我们注射了使用慢病毒介导的CD19嵌合抗原受体(CTL019)修饰的自体T细胞到复发性难治性急性淋巴白血病患者体内(浓度为0.76×106 to 20.6×106个CTL019细胞每公斤体重)。检测病人的反应、毒副作用以及体内循环的CTL019T细胞的扩增和持续作用。
结果:
共有30个儿童和成人接受了CTL019细胞的治疗。27个病人(90%)有完全的缓解,包含2个难治性病人和15个已经干细胞移植的病人。CTL019细胞在体内增殖并且在病人体内的血液、骨髓和脑脊液中被检测到。具有持续的缓解,六个月无进展生存率达到67%95%可信区间[CI]5188),和一个总生存率78%95%可信区间CI65 - 95)。6个月时,体内持续存在T细胞的病人比例在68%95% CI5092),病人无复发B细胞发育不全的比例在73% (95% CI, 57 to 94)。所有患者均具有细胞因子释放综合征。严重的细胞因子综合症,会在27%的病人中发展,在注射前会有一个更高的疾病负担,使用IL-6受体抗体tocilizumab治疗会有有效的治疗。
结论:
靶向CD19嵌合抗原受体修饰的T细胞治疗在治疗复发难治性ALL中是有效果的。CTL1019与高缓解率有关,甚至在干细胞移植失败的病人中也有效,以及长达24个月的持续缓解作用也能够被观察到。
出自爱康得生物技术

Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia 2015.12.2.pdf

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