Next-day manufacture of a novel anti-CD19 CAR-T therapy for B-cell acute lymphoblastic leukemia: first-in-human clinical study
Abstract To improve clinical outcomes and shorten the vein-to-vein time of chimeric antigen receptor T (CAR-T) cells, we developed the FasT CAR-T (F-CAR-T) next-day manufacturing platform. We report the preclinical and first-in-human clinical studies evaluating the safety, feasibility, and prelimina...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-07-01
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| Series: | Blood Cancer Journal |
| Online Access: | https://doi.org/10.1038/s41408-022-00694-6 |
| _version_ | 1811219112994537472 |
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| author | Junfang Yang Jiaping He Xian Zhang Jingjing Li Zhenguang Wang Yongliang Zhang Liyuan Qiu Qionglu Wu Zhe Sun Xun Ye Wenjie Yin Wei Cao Lianjun Shen Martina Sersch Peihua Lu |
| author_facet | Junfang Yang Jiaping He Xian Zhang Jingjing Li Zhenguang Wang Yongliang Zhang Liyuan Qiu Qionglu Wu Zhe Sun Xun Ye Wenjie Yin Wei Cao Lianjun Shen Martina Sersch Peihua Lu |
| author_sort | Junfang Yang |
| collection | DOAJ |
| description | Abstract To improve clinical outcomes and shorten the vein-to-vein time of chimeric antigen receptor T (CAR-T) cells, we developed the FasT CAR-T (F-CAR-T) next-day manufacturing platform. We report the preclinical and first-in-human clinical studies evaluating the safety, feasibility, and preliminary efficacy of CD19 F-CAR-T in B-cell acute lymphoblastic leukemia (B-ALL). CD19 F-CAR-T cells demonstrated excellent proliferation with a younger cellular phenotype, less exhaustion, and more effective tumor elimination compared to conventional CAR-T cells in the preclinical study. In our phase I study (NCT03825718), F-CAR-T cells were successfully manufactured and infused in all of the 25 enrolled pediatric and adult patients with B-ALL. CD19 F-CAR-T safety profile was manageable with 24% grade 3 cytokine release syndrome (CRS) and 28% grade 3/4 neurotoxicity occurring predominantly in pediatric patients. On day 14, 23/25 patients achieved minimal residual disease (MRD)-negative complete remission (CR), and 20 subsequently underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) within 3 months post F-CAR-T therapy. Fifteen of 20 patients were disease-free with a median remission duration of 734 days. One patient relapsed and 4/20 died from transplant-related mortality. Of the three patients who did not undergo allo-HSCT, two remained in CR until 10 months post-F-CAR-T. Our data indicate that anti-CD19 FasT CAR-T shows promising early efficacy for B-ALL. Further evaluations in larger clinical studies are needed. |
| first_indexed | 2024-04-12T07:20:57Z |
| format | Article |
| id | doaj.art-da22bfd282e44f20ae31418d9a9eb4eb |
| institution | Directory Open Access Journal |
| issn | 2044-5385 |
| language | English |
| last_indexed | 2024-04-12T07:20:57Z |
| publishDate | 2022-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Blood Cancer Journal |
| spelling | doaj.art-da22bfd282e44f20ae31418d9a9eb4eb2022-12-22T03:42:20ZengNature Publishing GroupBlood Cancer Journal2044-53852022-07-011271910.1038/s41408-022-00694-6Next-day manufacture of a novel anti-CD19 CAR-T therapy for B-cell acute lymphoblastic leukemia: first-in-human clinical studyJunfang Yang0Jiaping He1Xian Zhang2Jingjing Li3Zhenguang Wang4Yongliang Zhang5Liyuan Qiu6Qionglu Wu7Zhe Sun8Xun Ye9Wenjie Yin10Wei Cao11Lianjun Shen12Martina Sersch13Peihua Lu14Hebei Yanda Lu Daopei HospitalGracell Biotechnologies Co., LtdHebei Yanda Lu Daopei HospitalHebei Yanda Lu Daopei HospitalGracell Biotechnologies Co., LtdGracell Biotechnologies Co., LtdHebei Yanda Lu Daopei HospitalGracell Biotechnologies Co., LtdGracell Biotechnologies Co., LtdGracell Biotechnologies Co., LtdGracell Biotechnologies Co., LtdGracell Biotechnologies Co., LtdGracell Biotechnologies Co., LtdGracell Biotechnologies Co., LtdHebei Yanda Lu Daopei HospitalAbstract To improve clinical outcomes and shorten the vein-to-vein time of chimeric antigen receptor T (CAR-T) cells, we developed the FasT CAR-T (F-CAR-T) next-day manufacturing platform. We report the preclinical and first-in-human clinical studies evaluating the safety, feasibility, and preliminary efficacy of CD19 F-CAR-T in B-cell acute lymphoblastic leukemia (B-ALL). CD19 F-CAR-T cells demonstrated excellent proliferation with a younger cellular phenotype, less exhaustion, and more effective tumor elimination compared to conventional CAR-T cells in the preclinical study. In our phase I study (NCT03825718), F-CAR-T cells were successfully manufactured and infused in all of the 25 enrolled pediatric and adult patients with B-ALL. CD19 F-CAR-T safety profile was manageable with 24% grade 3 cytokine release syndrome (CRS) and 28% grade 3/4 neurotoxicity occurring predominantly in pediatric patients. On day 14, 23/25 patients achieved minimal residual disease (MRD)-negative complete remission (CR), and 20 subsequently underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) within 3 months post F-CAR-T therapy. Fifteen of 20 patients were disease-free with a median remission duration of 734 days. One patient relapsed and 4/20 died from transplant-related mortality. Of the three patients who did not undergo allo-HSCT, two remained in CR until 10 months post-F-CAR-T. Our data indicate that anti-CD19 FasT CAR-T shows promising early efficacy for B-ALL. Further evaluations in larger clinical studies are needed.https://doi.org/10.1038/s41408-022-00694-6 |
| spellingShingle | Junfang Yang Jiaping He Xian Zhang Jingjing Li Zhenguang Wang Yongliang Zhang Liyuan Qiu Qionglu Wu Zhe Sun Xun Ye Wenjie Yin Wei Cao Lianjun Shen Martina Sersch Peihua Lu Next-day manufacture of a novel anti-CD19 CAR-T therapy for B-cell acute lymphoblastic leukemia: first-in-human clinical study Blood Cancer Journal |
| title | Next-day manufacture of a novel anti-CD19 CAR-T therapy for B-cell acute lymphoblastic leukemia: first-in-human clinical study |
| title_full | Next-day manufacture of a novel anti-CD19 CAR-T therapy for B-cell acute lymphoblastic leukemia: first-in-human clinical study |
| title_fullStr | Next-day manufacture of a novel anti-CD19 CAR-T therapy for B-cell acute lymphoblastic leukemia: first-in-human clinical study |
| title_full_unstemmed | Next-day manufacture of a novel anti-CD19 CAR-T therapy for B-cell acute lymphoblastic leukemia: first-in-human clinical study |
| title_short | Next-day manufacture of a novel anti-CD19 CAR-T therapy for B-cell acute lymphoblastic leukemia: first-in-human clinical study |
| title_sort | next day manufacture of a novel anti cd19 car t therapy for b cell acute lymphoblastic leukemia first in human clinical study |
| url | https://doi.org/10.1038/s41408-022-00694-6 |
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