Efficacy and safety of a novel CD19, CD22 dual-targeted fully human loop bi-CAR-T for the treatment of relapsed/refractory B cell non-Hodgkin lymphoma
Abstract Background Chimeric antigen receptor (CAR) T-cell therapies targeting CD19 have demonstrated promising efficacy in treating refractory or relapsed B-cell malignancies. Nonetheless, challenges such as antigen escape-mediated relapse and toxicities, including cytokine release syndrome (CRS) a...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-06-01
|
| Series: | Journal of Translational Medicine |
| Online Access: | https://doi.org/10.1186/s12967-025-06567-3 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850224343956586496 |
|---|---|
| author | Hanyu Wang Gaoxiang Wang Tongjuan Li Peiling Zhang Zekai Mao Hui Luo Xiaojian Zhu Dengju Li Jianfeng Zhou Xiaoxi Zhou Liang Huang |
| author_facet | Hanyu Wang Gaoxiang Wang Tongjuan Li Peiling Zhang Zekai Mao Hui Luo Xiaojian Zhu Dengju Li Jianfeng Zhou Xiaoxi Zhou Liang Huang |
| author_sort | Hanyu Wang |
| collection | DOAJ |
| description | Abstract Background Chimeric antigen receptor (CAR) T-cell therapies targeting CD19 have demonstrated promising efficacy in treating refractory or relapsed B-cell malignancies. Nonetheless, challenges such as antigen escape-mediated relapse and toxicities, including cytokine release syndrome (CRS) and neurotoxicity, may impede their clinical application. Methods In this study, we developed a fully human, bivalent loop bi-CAR-T targeting both CD19 and CD22 (CT120). We conducted an open-label, single-center, single-arm phase I/II trial to evaluate the efficacy and safety of CT120 in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL). Results The overall response rate (ORR) was 65.2%, with 56.5% of patients achieving a complete response. The median progression-free survival (PFS) was 23.95 months, and the median overall survival (OS) was not reached. The 12-month PFS rate was 54.66%, and the 12-month OS rate was 77.34%. The 24-month PFS rate was 49.69% and the 24-month OS rate was 72.51%. Prognostic factors for poorer outcomes included bulky mass, high international prognostic index (IPI), multiple extranodal lesions, or MYD88 mutation. No loss of CD19/CD22 expression was observed in patients with relapse. Grade 3 or higher CRS occurred in only one patient (4.3%), and no immune effector cell-associated neurotoxicity syndrome (ICANS) was seen. Notably, we observed both early and late immune effector cell-associated hematotoxicity (ICAHT) following CT120 infusion. Late-onset neutropenia (after day 30) occurred in 78.3% of patients, and severe anemia was correlated with worse prognosis. Conclusions Overall, CT120 infusion is effective, safe, and reliable for reducing antigen escape-related relapse in patients with relapsed or refractory NHL. Trial registration Chinese Clinical Trial Registry (ChiCTR), ChiCTR2000038641). Registered 26 September 2020, https://www.chictr.org.cn/showproj.html?proj=61780 . |
| format | Article |
| id | doaj-art-c3c90f95bd584071ac8a74da43658287 |
| institution | OA Journals |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-c3c90f95bd584071ac8a74da436582872025-08-20T02:05:39ZengBMCJournal of Translational Medicine1479-58762025-06-0123111310.1186/s12967-025-06567-3Efficacy and safety of a novel CD19, CD22 dual-targeted fully human loop bi-CAR-T for the treatment of relapsed/refractory B cell non-Hodgkin lymphomaHanyu Wang0Gaoxiang Wang1Tongjuan Li2Peiling Zhang3Zekai Mao4Hui Luo5Xiaojian Zhu6Dengju Li7Jianfeng Zhou8Xiaoxi Zhou9Liang Huang10Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyState Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, National Clinical Research Center for Blood Diseases, Chinese Academy of Medical Science & Peking Union Medical CollegeAbstract Background Chimeric antigen receptor (CAR) T-cell therapies targeting CD19 have demonstrated promising efficacy in treating refractory or relapsed B-cell malignancies. Nonetheless, challenges such as antigen escape-mediated relapse and toxicities, including cytokine release syndrome (CRS) and neurotoxicity, may impede their clinical application. Methods In this study, we developed a fully human, bivalent loop bi-CAR-T targeting both CD19 and CD22 (CT120). We conducted an open-label, single-center, single-arm phase I/II trial to evaluate the efficacy and safety of CT120 in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL). Results The overall response rate (ORR) was 65.2%, with 56.5% of patients achieving a complete response. The median progression-free survival (PFS) was 23.95 months, and the median overall survival (OS) was not reached. The 12-month PFS rate was 54.66%, and the 12-month OS rate was 77.34%. The 24-month PFS rate was 49.69% and the 24-month OS rate was 72.51%. Prognostic factors for poorer outcomes included bulky mass, high international prognostic index (IPI), multiple extranodal lesions, or MYD88 mutation. No loss of CD19/CD22 expression was observed in patients with relapse. Grade 3 or higher CRS occurred in only one patient (4.3%), and no immune effector cell-associated neurotoxicity syndrome (ICANS) was seen. Notably, we observed both early and late immune effector cell-associated hematotoxicity (ICAHT) following CT120 infusion. Late-onset neutropenia (after day 30) occurred in 78.3% of patients, and severe anemia was correlated with worse prognosis. Conclusions Overall, CT120 infusion is effective, safe, and reliable for reducing antigen escape-related relapse in patients with relapsed or refractory NHL. Trial registration Chinese Clinical Trial Registry (ChiCTR), ChiCTR2000038641). Registered 26 September 2020, https://www.chictr.org.cn/showproj.html?proj=61780 .https://doi.org/10.1186/s12967-025-06567-3 |
| spellingShingle | Hanyu Wang Gaoxiang Wang Tongjuan Li Peiling Zhang Zekai Mao Hui Luo Xiaojian Zhu Dengju Li Jianfeng Zhou Xiaoxi Zhou Liang Huang Efficacy and safety of a novel CD19, CD22 dual-targeted fully human loop bi-CAR-T for the treatment of relapsed/refractory B cell non-Hodgkin lymphoma Journal of Translational Medicine |
| title | Efficacy and safety of a novel CD19, CD22 dual-targeted fully human loop bi-CAR-T for the treatment of relapsed/refractory B cell non-Hodgkin lymphoma |
| title_full | Efficacy and safety of a novel CD19, CD22 dual-targeted fully human loop bi-CAR-T for the treatment of relapsed/refractory B cell non-Hodgkin lymphoma |
| title_fullStr | Efficacy and safety of a novel CD19, CD22 dual-targeted fully human loop bi-CAR-T for the treatment of relapsed/refractory B cell non-Hodgkin lymphoma |
| title_full_unstemmed | Efficacy and safety of a novel CD19, CD22 dual-targeted fully human loop bi-CAR-T for the treatment of relapsed/refractory B cell non-Hodgkin lymphoma |
| title_short | Efficacy and safety of a novel CD19, CD22 dual-targeted fully human loop bi-CAR-T for the treatment of relapsed/refractory B cell non-Hodgkin lymphoma |
| title_sort | efficacy and safety of a novel cd19 cd22 dual targeted fully human loop bi car t for the treatment of relapsed refractory b cell non hodgkin lymphoma |
| url | https://doi.org/10.1186/s12967-025-06567-3 |
| work_keys_str_mv | AT hanyuwang efficacyandsafetyofanovelcd19cd22dualtargetedfullyhumanloopbicartforthetreatmentofrelapsedrefractorybcellnonhodgkinlymphoma AT gaoxiangwang efficacyandsafetyofanovelcd19cd22dualtargetedfullyhumanloopbicartforthetreatmentofrelapsedrefractorybcellnonhodgkinlymphoma AT tongjuanli efficacyandsafetyofanovelcd19cd22dualtargetedfullyhumanloopbicartforthetreatmentofrelapsedrefractorybcellnonhodgkinlymphoma AT peilingzhang efficacyandsafetyofanovelcd19cd22dualtargetedfullyhumanloopbicartforthetreatmentofrelapsedrefractorybcellnonhodgkinlymphoma AT zekaimao efficacyandsafetyofanovelcd19cd22dualtargetedfullyhumanloopbicartforthetreatmentofrelapsedrefractorybcellnonhodgkinlymphoma AT huiluo efficacyandsafetyofanovelcd19cd22dualtargetedfullyhumanloopbicartforthetreatmentofrelapsedrefractorybcellnonhodgkinlymphoma AT xiaojianzhu efficacyandsafetyofanovelcd19cd22dualtargetedfullyhumanloopbicartforthetreatmentofrelapsedrefractorybcellnonhodgkinlymphoma AT dengjuli efficacyandsafetyofanovelcd19cd22dualtargetedfullyhumanloopbicartforthetreatmentofrelapsedrefractorybcellnonhodgkinlymphoma AT jianfengzhou efficacyandsafetyofanovelcd19cd22dualtargetedfullyhumanloopbicartforthetreatmentofrelapsedrefractorybcellnonhodgkinlymphoma AT xiaoxizhou efficacyandsafetyofanovelcd19cd22dualtargetedfullyhumanloopbicartforthetreatmentofrelapsedrefractorybcellnonhodgkinlymphoma AT lianghuang efficacyandsafetyofanovelcd19cd22dualtargetedfullyhumanloopbicartforthetreatmentofrelapsedrefractorybcellnonhodgkinlymphoma |