Novel CD19 chimeric antigen receptor T cells manufactured next-day for acute lymphoblastic leukemia
Abstract Chimeric antigen receptor-engineered T (CAR-T) cells have shown promising efficacy in patients with relapsed/refractory B cell acute lymphoblastic leukemia (R/R B-ALL). However, challenges remain including long manufacturing processes that need to be overcome. We presented the CD19-targetin...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-06-01
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| Series: | Blood Cancer Journal |
| Online Access: | https://doi.org/10.1038/s41408-022-00688-4 |
| _version_ | 1811333810223054848 |
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| author | Cheng Zhang Jiaping He Li Liu Jishi Wang Sanbin Wang Ligen Liu Jian Ge Lei Gao Li Gao Peiyan Kong Yao Liu Jia Liu Yu Han Yongliang Zhang Zhe Sun Xun Ye Wenjie Yin Martina Sersch Lianjun Shen Wei William Cao Xi Zhang |
| author_facet | Cheng Zhang Jiaping He Li Liu Jishi Wang Sanbin Wang Ligen Liu Jian Ge Lei Gao Li Gao Peiyan Kong Yao Liu Jia Liu Yu Han Yongliang Zhang Zhe Sun Xun Ye Wenjie Yin Martina Sersch Lianjun Shen Wei William Cao Xi Zhang |
| author_sort | Cheng Zhang |
| collection | DOAJ |
| description | Abstract Chimeric antigen receptor-engineered T (CAR-T) cells have shown promising efficacy in patients with relapsed/refractory B cell acute lymphoblastic leukemia (R/R B-ALL). However, challenges remain including long manufacturing processes that need to be overcome. We presented the CD19-targeting CAR-T cell product GC007F manufactured next-day (FasTCAR-T cells) and administered to patients with R/R B-ALL. A total of 21 patients over 14 years of age with CD19+ R/R B-ALL were screened, enrolled and infused with a single infusion of GC007F CAR-T at three different dose levels. The primary objective of the study was to assess safety, secondary objectives included pharmacokinetics of GC007F cells in patients with R/R B-ALL and preliminary efficacy. We were able to demonstrate in preclinical studies that GC007F cells exhibited better proliferation and tumor killing than conventional CAR-T (C-CAR-T) cells. In this investigator-initiated study all 18 efficacy-evaluable patients achieved a complete remission (CR) (18/18, 100.00%) by day 28, with 17 of the patients (94.4%) achieving CR with minimal residual disease (MRD) negative. Fifteen (83.3%) remained disease free at the 3-month assessment, 14 patients (77.8%) maintaining MRD negative at month 3. Among all 21 enrolled patients, the median peak of CAR-T cell was on day 10, with a median peak copy number of 104899.5/µg DNA and a median persistence period of 56 days (range: 7–327 days). The incidence of cytokine release syndrome (CRS) was 95.2% (n = 20), with severe CRS occurring in 52.4% (n = 11) of the patients. Six patients (28.6%) developed neurotoxicity of any grade. GC007F demonstrated superior expansion capacity and a less exhausted phenotype as compared to (C-CAR-T) cells. Moreover, this first-in-human clinical study showed that the novel, next-day manufacturing FasTCAR-T cells was feasible with a manageable toxicity profile in patients with R/R B-ALL. |
| first_indexed | 2024-04-13T16:58:24Z |
| format | Article |
| id | doaj.art-1b42782d65094bf98c5c91e35d02ba8f |
| institution | Directory Open Access Journal |
| issn | 2044-5385 |
| language | English |
| last_indexed | 2024-04-13T16:58:24Z |
| publishDate | 2022-06-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Blood Cancer Journal |
| spelling | doaj.art-1b42782d65094bf98c5c91e35d02ba8f2022-12-22T02:38:44ZengNature Publishing GroupBlood Cancer Journal2044-53852022-06-011261910.1038/s41408-022-00688-4Novel CD19 chimeric antigen receptor T cells manufactured next-day for acute lymphoblastic leukemiaCheng Zhang0Jiaping He1Li Liu2Jishi Wang3Sanbin Wang4Ligen Liu5Jian Ge6Lei Gao7Li Gao8Peiyan Kong9Yao Liu10Jia Liu11Yu Han12Yongliang Zhang13Zhe Sun14Xun Ye15Wenjie Yin16Martina Sersch17Lianjun Shen18Wei William Cao19Xi Zhang20Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, Burn and Combined Injury, Army Medical UniversityGracell Biotechnologies LtdDepartment of Hematology, Tangdu Hospital, Air Force Medical UniversityDepartment of Hematology, The Affiliated Hospital of Guizhou Medical UniversityDepartment of Hematology, 920th Hospital of Joint Logistics Support ForceDepartment of Hematology, Tongren Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Hematology, The First Affiliated Hospital of Anhui Medical UniversityMedical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, Burn and Combined Injury, Army Medical UniversityMedical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, Burn and Combined Injury, Army Medical UniversityMedical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, Burn and Combined Injury, Army Medical UniversityMedical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, Burn and Combined Injury, Army Medical UniversityGracell Biotechnologies LtdGracell Biotechnologies LtdGracell Biotechnologies LtdGracell Biotechnologies LtdGracell Biotechnologies LtdGracell Biotechnologies LtdGracell Biotechnologies LtdGracell Biotechnologies LtdGracell Biotechnologies LtdMedical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, Burn and Combined Injury, Army Medical UniversityAbstract Chimeric antigen receptor-engineered T (CAR-T) cells have shown promising efficacy in patients with relapsed/refractory B cell acute lymphoblastic leukemia (R/R B-ALL). However, challenges remain including long manufacturing processes that need to be overcome. We presented the CD19-targeting CAR-T cell product GC007F manufactured next-day (FasTCAR-T cells) and administered to patients with R/R B-ALL. A total of 21 patients over 14 years of age with CD19+ R/R B-ALL were screened, enrolled and infused with a single infusion of GC007F CAR-T at three different dose levels. The primary objective of the study was to assess safety, secondary objectives included pharmacokinetics of GC007F cells in patients with R/R B-ALL and preliminary efficacy. We were able to demonstrate in preclinical studies that GC007F cells exhibited better proliferation and tumor killing than conventional CAR-T (C-CAR-T) cells. In this investigator-initiated study all 18 efficacy-evaluable patients achieved a complete remission (CR) (18/18, 100.00%) by day 28, with 17 of the patients (94.4%) achieving CR with minimal residual disease (MRD) negative. Fifteen (83.3%) remained disease free at the 3-month assessment, 14 patients (77.8%) maintaining MRD negative at month 3. Among all 21 enrolled patients, the median peak of CAR-T cell was on day 10, with a median peak copy number of 104899.5/µg DNA and a median persistence period of 56 days (range: 7–327 days). The incidence of cytokine release syndrome (CRS) was 95.2% (n = 20), with severe CRS occurring in 52.4% (n = 11) of the patients. Six patients (28.6%) developed neurotoxicity of any grade. GC007F demonstrated superior expansion capacity and a less exhausted phenotype as compared to (C-CAR-T) cells. Moreover, this first-in-human clinical study showed that the novel, next-day manufacturing FasTCAR-T cells was feasible with a manageable toxicity profile in patients with R/R B-ALL.https://doi.org/10.1038/s41408-022-00688-4 |
| spellingShingle | Cheng Zhang Jiaping He Li Liu Jishi Wang Sanbin Wang Ligen Liu Jian Ge Lei Gao Li Gao Peiyan Kong Yao Liu Jia Liu Yu Han Yongliang Zhang Zhe Sun Xun Ye Wenjie Yin Martina Sersch Lianjun Shen Wei William Cao Xi Zhang Novel CD19 chimeric antigen receptor T cells manufactured next-day for acute lymphoblastic leukemia Blood Cancer Journal |
| title | Novel CD19 chimeric antigen receptor T cells manufactured next-day for acute lymphoblastic leukemia |
| title_full | Novel CD19 chimeric antigen receptor T cells manufactured next-day for acute lymphoblastic leukemia |
| title_fullStr | Novel CD19 chimeric antigen receptor T cells manufactured next-day for acute lymphoblastic leukemia |
| title_full_unstemmed | Novel CD19 chimeric antigen receptor T cells manufactured next-day for acute lymphoblastic leukemia |
| title_short | Novel CD19 chimeric antigen receptor T cells manufactured next-day for acute lymphoblastic leukemia |
| title_sort | novel cd19 chimeric antigen receptor t cells manufactured next day for acute lymphoblastic leukemia |
| url | https://doi.org/10.1038/s41408-022-00688-4 |
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