使用局部生产的抗cd19 CAR-T细胞治疗成人复发/难治性b细胞淋巴瘤

Q4 Medicine

Oncogematologiya Pub Date : 2023-09-11 DOI:10.17650/1818-8346-2023-18-3-26-34

N. E. Konoplya, O. A. Kalenik, I. N. Severin, A. A. Savritskaya, N. M. Bobrova, T. M. Doroshenko, A. S. Portyanko

{"title":"使用局部生产的抗cd19 CAR-T细胞治疗成人复发/难治性b细胞淋巴瘤","authors":"N. E. Konoplya, O. A. Kalenik, I. N. Severin, A. A. Savritskaya, N. M. Bobrova, T. M. Doroshenko, A. S. Portyanko","doi":"10.17650/1818-8346-2023-18-3-26-34","DOIUrl":null,"url":null,"abstract":"Background. Patients with B-cell lymphoma have an extremely unfavorable prognosis after relapse or in case of refractoriness to the first and consecutive lines of immunochemotherapy with the anti-CD19 CAR-T cells being the only therapeutic option to such patients. the manual preparation of anti-CD19 CAR-T lymphocytes was reproduced in the N. N. Alexandrov republican research and practical center for oncology and medical radiology (Minsk). Their safety was demonstrated. Aim. To estimate safety, tolerability and efficacy of the in-house CAR-T cells, including objective response rate, progression-free and overall survival. Materials and methods. The second generation anti-CD19 chimeric antigen receptor contained an anti-CD19 antibody scFv fragment, CD28 transmembrane domain, 4-1BB and CD3z signaling domains. the coding sequence was cloned into the lentiviral vector S4. The cell product was obtained by expansion of CD4- and CD8-positive lymphocytes populations with IL-7 and IL-15 after initial activation and lentiviral transduction with vector S4. CAR-T cells were infused into 8 patients with refractory forms of B-cell lymphoma after the preliminary lymphodepleting chemotherapy. Persistence of CAR-T cells was assessed by flow cytometry. therapeutic efficiency was assessed by positron emission tomography-computed tomography with 18 F-fluorodeoxyglucose. Results. Expansion of CAR-T cells with resulting b-cell aplasia was observed in all patients. the median of observation was 113 days (range 22–529 days). objective response rate was 100 %, complete remission was observed in 6 patients, partial response – in 1 patient. One patient died because of complications before the clinical response. Overall survival was 88 ± 12 %. cytokine release syndrome and neurotoxicity were not observed in 6 out of 8 patients despite a high tumor burden. Conclusion. Our study demonstrated efficiency and safety of the in-house CAR-T cells for the treatment of patients with refractory B-cell lymphomas.","PeriodicalId":37536,"journal":{"name":"Oncogematologiya","volume":"46 1","pages":"0"},"PeriodicalIF":0.0000,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Use of locally produced anti-CD19 CAR-T cells in the treatment of relapsed/refractory B-cell lymphomas in adults\",\"authors\":\"N. E. Konoplya, O. A. Kalenik, I. N. Severin, A. A. Savritskaya, N. M. Bobrova, T. M. Doroshenko, A. S. Portyanko\",\"doi\":\"10.17650/1818-8346-2023-18-3-26-34\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Background. Patients with B-cell lymphoma have an extremely unfavorable prognosis after relapse or in case of refractoriness to the first and consecutive lines of immunochemotherapy with the anti-CD19 CAR-T cells being the only therapeutic option to such patients. the manual preparation of anti-CD19 CAR-T lymphocytes was reproduced in the N. N. Alexandrov republican research and practical center for oncology and medical radiology (Minsk). Their safety was demonstrated. Aim. To estimate safety, tolerability and efficacy of the in-house CAR-T cells, including objective response rate, progression-free and overall survival. Materials and methods. The second generation anti-CD19 chimeric antigen receptor contained an anti-CD19 antibody scFv fragment, CD28 transmembrane domain, 4-1BB and CD3z signaling domains. the coding sequence was cloned into the lentiviral vector S4. The cell product was obtained by expansion of CD4- and CD8-positive lymphocytes populations with IL-7 and IL-15 after initial activation and lentiviral transduction with vector S4. CAR-T cells were infused into 8 patients with refractory forms of B-cell lymphoma after the preliminary lymphodepleting chemotherapy. Persistence of CAR-T cells was assessed by flow cytometry. therapeutic efficiency was assessed by positron emission tomography-computed tomography with 18 F-fluorodeoxyglucose. Results. Expansion of CAR-T cells with resulting b-cell aplasia was observed in all patients. the median of observation was 113 days (range 22–529 days). objective response rate was 100 %, complete remission was observed in 6 patients, partial response – in 1 patient. One patient died because of complications before the clinical response. Overall survival was 88 ± 12 %. cytokine release syndrome and neurotoxicity were not observed in 6 out of 8 patients despite a high tumor burden. Conclusion. Our study demonstrated efficiency and safety of the in-house CAR-T cells for the treatment of patients with refractory B-cell lymphomas.\",\"PeriodicalId\":37536,\"journal\":{\"name\":\"Oncogematologiya\",\"volume\":\"46 1\",\"pages\":\"0\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-09-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Oncogematologiya\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.17650/1818-8346-2023-18-3-26-34\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oncogematologiya","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.17650/1818-8346-2023-18-3-26-34","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"Medicine","Score":null,"Total":0}

引用次数: 0

摘要

背景。b细胞淋巴瘤患者在复发后或在第一次和连续免疫化疗难治性的情况下预后极其不利，抗cd19 CAR-T细胞是这类患者唯一的治疗选择。人工制备抗cd19 CAR-T淋巴细胞在N. N.亚历山德罗夫共和国肿瘤和医学放射学研究和实践中心(明斯克)进行了复制。他们的安全得到了证明。的目标。评估内部CAR-T细胞的安全性、耐受性和有效性，包括客观缓解率、无进展和总生存期。材料和方法。第二代抗cd19嵌合抗原受体含有抗cd19抗体scFv片段、CD28跨膜结构域、4-1BB和CD3z信号域。将编码序列克隆到慢病毒载体S4中。细胞产物是通过IL-7和IL-15初始激活后扩增CD4和cd8阳性淋巴细胞群，并用载体S4慢病毒转导获得的。CAR-T细胞被输注到8例难治性b细胞淋巴瘤患者的初步淋巴细胞耗尽化疗后。通过流式细胞术评估CAR-T细胞的持久性。采用正电子发射断层扫描- 18f -氟脱氧葡萄糖计算机断层扫描评估治疗效果。结果。在所有患者中都观察到CAR-T细胞扩增导致b细胞发育不全。观察时间中位数为113天(22-529天)。客观有效率为100%，完全缓解6例，部分缓解1例。1例患者在临床反应前因并发症死亡。总生存率为88±12%。8例患者中有6例没有观察到细胞因子释放综合征和神经毒性，尽管肿瘤负担很高。结论。我们的研究证明了内部CAR-T细胞治疗难治性b细胞淋巴瘤的有效性和安全性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Use of locally produced anti-CD19 CAR-T cells in the treatment of relapsed/refractory B-cell lymphomas in adults

Background. Patients with B-cell lymphoma have an extremely unfavorable prognosis after relapse or in case of refractoriness to the first and consecutive lines of immunochemotherapy with the anti-CD19 CAR-T cells being the only therapeutic option to such patients. the manual preparation of anti-CD19 CAR-T lymphocytes was reproduced in the N. N. Alexandrov republican research and practical center for oncology and medical radiology (Minsk). Their safety was demonstrated. Aim. To estimate safety, tolerability and efficacy of the in-house CAR-T cells, including objective response rate, progression-free and overall survival. Materials and methods. The second generation anti-CD19 chimeric antigen receptor contained an anti-CD19 antibody scFv fragment, CD28 transmembrane domain, 4-1BB and CD3z signaling domains. the coding sequence was cloned into the lentiviral vector S4. The cell product was obtained by expansion of CD4- and CD8-positive lymphocytes populations with IL-7 and IL-15 after initial activation and lentiviral transduction with vector S4. CAR-T cells were infused into 8 patients with refractory forms of B-cell lymphoma after the preliminary lymphodepleting chemotherapy. Persistence of CAR-T cells was assessed by flow cytometry. therapeutic efficiency was assessed by positron emission tomography-computed tomography with 18 F-fluorodeoxyglucose. Results. Expansion of CAR-T cells with resulting b-cell aplasia was observed in all patients. the median of observation was 113 days (range 22–529 days). objective response rate was 100 %, complete remission was observed in 6 patients, partial response – in 1 patient. One patient died because of complications before the clinical response. Overall survival was 88 ± 12 %. cytokine release syndrome and neurotoxicity were not observed in 6 out of 8 patients despite a high tumor burden. Conclusion. Our study demonstrated efficiency and safety of the in-house CAR-T cells for the treatment of patients with refractory B-cell lymphomas.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Oncogematologiya Medicine-Hematology

CiteScore

0.50

自引率

0.00%

发文量

审稿时长

10 weeks

期刊介绍： The main purpose of the Oncohematology journal is to publish up-to-date information on clinical, experimental and fundamental scientific research, diagnostics and treatment options, as well as other materials on all relevant issues in oncohematology. The journal’s objectives are to inform various specialists who provide advisory and therapeutic assistance to patients with oncohematological diseases about current advances, including the latest methods for the diagnosis and treatment of malignant blood diseases. The journal is an interdisciplinary scientific publication uniting doctors of various specialties ‒ hematologists, oncologists, surgeons, radiation therapists, intensive care specialist, pathologists, etc. ‒ to form an interdisciplinary therapy approach in order to improve the treatment efficacy of patients with hematological malignancies.