Long-Term Safety and Efficacy of CD19 Humanized Selective CAR-T Therapy in B-ALL Patients Who Have Previously Received Murine-Based CD19 CAR-T Therapy.
Long-Term Safety and Efficacy of CD19 Humanized Selective CAR-T Therapy in B-ALL Patients Who Have Previously Received Murine-Based CD19 CAR-T Therapy.
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DOI：
10.3389/fonc.2022.884782
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发表时间：
2022
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
基于小鼠的CD19 CAR-T （CD19m CAR-T）疗法首次用于B-ALL患者时可导致相对较高的CR率。然而，DOR并不理想，一部分患者甚至表现出对CD19m CAR-T的原发性耐药。为了解决这些问题，我们采用了一种人源化的选择性CD19CAR-T (CD19hs CAR-T)，并评估了8例在CD19m CAR-T输注后复发或未能达到CR的R/R B-ALL患者的长期安全性和有效性（临床试验编号：ChiCTR1800014761和ChiCTR1800017439）。8例患者中，7例在第一次输注CD19hs CAR-T后第30天达到CR。中位CRS评分为1,8例患者均未见明显神经毒性。中位DOR为11个月，明显长于CD19mCAR-T输注后的DOR。抗car抗体在先前接受过CD19m CAR-T输注的患者中被诱导，但在那些接受过一次或多次cd19hcar - t治疗的患者中没有被诱导，这可能是导致这些患者的次优DOR和/或有效反应失败的原因。相比之下，与CD19m CAR-T相比，CD19hs CAR-T诱导的免疫原性较低，这表明重复给药策略对于复发和/或对CD19m CAR-T治疗表现出原发性耐药的患者可能是可行和有效的。在本临床研究中，CD19hs CAR-T在既往接受过CD19m CAR-T治疗的R/R B-ALL患者中临床疗效显著，副作用轻微。(ChiCTR1800014761)。(ChiCTR1800017439)。
Murine-based CD19 CAR-T (CD19m CAR-T) therapy can lead to a relatively high CR rate when administered to B-ALL patients for the first time. However, the DOR is sub-optimal and a subset of patients even show primary resistance to CD19m CAR-T. To address these issues, we employed a humanized selective CD19CAR-T (CD19hs CAR-T) and evaluated the long-term safety and efficacy of treating 8 R/R B-ALL patients who had relapsed or failed to achieve CR following CD19m CAR-T infusion (Clinical trials’ number: ChiCTR1800014761 and ChiCTR1800017439). Of the 8 patients, 7 achieved CR on Day 30 after the 1st infusion of CD19hs CAR-T. The median CRS grade was 1 without significant neurotoxicity seen in any of the 8 patients. The median DOR was 11 months, significantly longer than the DOR following CD19mCAR-T infusions. Anti-CAR antibodies were induced in patients who had received prior CD19m CAR-T infusions but not in those following a single or repeated CD19hsCAR-T treatment, which probably had contributed to the sub-optimal DOR and/or failure of effective response in these patients. CD19hs CAR-T, in contrast, induced low immunogenicity compared with CD19m CAR-T, suggesting that a repeat dosing strategy might be feasible and efficacious for patients who have relapsed and/or show primary resistance to CD19m CAR-T therapy. In this clinical study, CD19hs CAR-T showed a significant clinical efficacy with mild side effect among patients with R/R B-ALL who had previously received CD19m CAR-T. (ChiCTR1800014761). (ChiCTR1800017439).
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患者特征对 B 细胞急性淋巴细胞白血病嵌合抗原受体 T 细胞治疗的影响
影响因子：
16.6
作者：
An F;Wang H;Liu Z;Wu F;Zhang J;Tao Q;Li Y;Shen Y;Ruan Y;Zhang Q;Pan Y;Zhu W;Qin H;Wang Y;Fu Y;Feng Z;Zhai Z
通讯作者：
Zhai Z
DOI：
10.1038/s41571-019-0184-6
发表时间：
2019-06
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Shah NN;Fry TJ
通讯作者：
Fry TJ
影响因子：
20.3
作者：
Jacoby, Elad;Yang, Yinmeng;Fry, Terry J.
通讯作者：
Fry, Terry J.
影响因子：
45.3
作者：
Shah, Nirali N.;Lee, Daniel W.;Mackall, Crystal L.
通讯作者：
Mackall, Crystal L.
影响因子：
5.1
作者：
Charrier, S.;Ferrand, M.;Galy, A.
通讯作者：
Galy, A.