This is a phase I, interventional, single-arm, open-label, dose-finding treatment study designed to evaluate the safety and efficacy of interleukin-7(IL-7) / interleukin-15 (IL-15) manufactured CAR T cells in adult patients with relapsed and/or refractory myeloma that have failed prior therapies.

开始日期2025-03-01

申办/合作机构

Medical College of Wisconsin

ChiCTR2100046374 / Recruiting临床1/2期IIT

To investigate the effectiveness and safety of up-front consolidation with BCMA-targeted CAR T-cell for newly diagnosed multiple myeloma

开始日期2021-05-15

申办/合作机构-

100 项与 BCMA-TGFβ CAR-T cells(Medical College of Wisconsin) 相关的临床结果

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100 项与 BCMA-TGFβ CAR-T cells(Medical College of Wisconsin) 相关的转化医学

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项与 BCMA-TGFβ CAR-T cells(Medical College of Wisconsin) 相关的文献（医药）

2024-09-23·Journal for immunotherapy of cancer

BCMA-BBZ-OX40 CAR-T Therapy Using an Instant Manufacturing Platform in Multiple Myeloma.

Article

作者: Bai, Jiefei ; Wu, Fei ; Li, Zhenling ; Ding, Yanping ; Yang, Yazi ; Liu, Hui ; Feng, Shi ; He, Ting ; Lu, Xinan ; Ma, Lie ; Wang, Ting ; Li, Jian ; Li, Jiangtao ; Liu, Guanghua ; Zhang, Chunli ; Feng, Ru

BACKGROUNDChimeric antigen receptor (CAR)-T cell has revolutionary efficacy against relapsed/refractory multiple myeloma (R/R MM). However, current CAR-T cell therapy has several limitations including long vein-to-vein time and limited viability.METHODSA 4-1BB-costimulated B-cell maturation antigen (BCMA) CAR-T integrating an independently-expressed OX40 (BCMA-BBZ-OX40) was designed and generated by a traditional manufacturing process (TraditionCART) or instant manufacturing platform (named InstanCART). The tumor-killing efficiency, differentiation, exhaustion, and expansion level were investigated in vitro and in tumor-bearing mice. An investigator-initiated clinical trial was performed in patients with R/R MM to evaluate the outcomes of both TraditionCART and InstanCART. The primary objective was safety within 1 month after CAR-T cell infusion. The secondary objective was the best overall response rate.RESULTSPreclinical studies revealed that integrated OX40 conferred BCMA CAR-T cells with superior cytotoxicity and reduced exhaustion levels. InstanCART process further enhanced the proliferation and T-cell stemness of BCMA-BBZ-OX40 CAR-T cells. BCMA-BBZ-OX40 CAR-T cells were successfully administered in 22 patients with R/R MM, including 15 patients with TraditionCART and 7 patients with InstanCART. Up to 50% (11/22) patients had a high-risk cytogenetic profile and 36% (8/22) had extramedullary disease. CAR-T therapy caused grade 1-2 cytokine release syndrome in 19/22 (80%) patients, grade 1 neurotoxicity in 2/22 (9%) patients and led to ≥grade 3 adverse events including neutropenia (20/22, 91%), thrombocytopenia (15/22, 68%), anemia (12/22, 55%), creatinine increased (1/22, 5%), hepatic enzymes increased (5/22, 23%), and sepsis (1/22, 5%). The best overall response rate was 100%, and 64% (14/22) of the patients had a complete response or better. The median manufacturing time was shorter for InstanCART therapy (3 days) than for TraditionCART therapy (10 days). Expansion and duration were dramatically higher for InstanCART cells than for TraditionCART cells.CONCLUSIONSBCMA-BBZ-OX40 CAR-T cells were well tolerated and exhibited potent responses in patients with R/R MM. InstanCART shortened the manufacturing period compared to TraditionCART, and improved the cellular kinetics. Our results demonstrated the potency and feasibility of OX40-modified BCMA CAR-T cells using InstanCART technology for R/R MM therapy.TRIAL REGISTRATION NUMBERThis trial was registered at www.CLINICALTRIALSgov as #NCT04537442.

2024-02-14·Science Translational Medicine1区 · 医学

Engineered T cells secreting anti-BCMA T cell engagers control multiple myeloma and promote immune memory in vivo

1区 · 医学

Article

作者: Gómez-Rosel, Marina ; Penela, Petronila ; Romencín, Paola A ; Bueno, Clara ; Pérez-Pons, Alba ; Río, Paula ; Mayado, Andrea ; Albitre, Ángela ; Jara, Maria ; Sanz, Laura ; Martín-Antonio, Beatriz ; Aguilar-Sopeña, Óscar ; Segura-Tudela, Alejandro ; Roda-Navarro, Pedro ; Blanco, Belén ; Jiménez-Reinoso, Anaïs ; Ramírez-Fernández, Ángel ; Orfao, Alberto ; Tapia-Galisteo, Antonio ; Martínez-López, Joaquín ; Perez-Amill, Lorena ; Díez-Alonso, Laura ; Anguita, Eduardo ; Martínez, Alba ; Hangiu, Oana ; Juan, Manel ; Menéndez, Pablo ; Valeri, Antonio ; Álvarez-Vallina, Luis ; Falgas, Aïda ; Solé, Francesc ; Rubio-Pérez, Laura ; Arroyo-Ródenas, Javier ; Almagro, Laura ; Domínguez-Alonso, Carmen ; García-Ortiz, Almudena

Multiple myeloma is the second most common hematological malignancy in adults and remains an incurable disease. B cell maturation antigen (BCMA)–directed immunotherapy, including T cells bearing chimeric antigen receptors (CARs) and systemically injected bispecific T cell engagers (TCEs), has shown remarkable clinical activity, and several products have received market approval. However, despite promising results, most patients eventually become refractory and relapse, highlighting the need for alternative strategies. Engineered T cells secreting TCE antibodies (STAb) represent a promising strategy that combines the advantages of adoptive cell therapies and bispecific antibodies. Here, we undertook a comprehensive preclinical study comparing the therapeutic potential of T cells either expressing second-generation anti-BCMA CARs (CAR-T) or secreting BCMAxCD3 TCEs (STAb-T) in a T cell–limiting experimental setting mimicking the conditions found in patients with relapsed/refractory multiple myeloma. STAb-T cells recruited T cell activity at extremely low effector-to-target ratios and were resistant to inhibition mediated by soluble BCMA released from the cell surface, resulting in enhanced cytotoxic responses and prevention of immune escape of multiple myeloma cells in vitro. These advantages led to robust expansion and persistence of STAb-T cells in vivo, generating long-lived memory BCMA-specific responses that could control multiple myeloma progression in xenograft models, outperforming traditional CAR-T cells. These promising preclinical results encourage clinical testing of the BCMA-STAb-T cell approach in relapsed/refractory multiple myeloma.

2023-06-01·Bone marrow transplantation

HBV reactivation in patients with chronic or resolved HBV infection following BCMA-targeted CAR-T cell therapy.

Article

作者: Cen, Zenan ; Jing, Ruirui ; Zhang, Yanlei ; Zhang, Mingming ; Chang, Alex H ; Lv, Yuqi ; Zheng, Haiqiong ; Hu, Yongxian ; Huang, He ; Cui, Jiazhen ; Ni, Fang ; Zhang, Qiqi ; Wei, Guoqing ; Zu, Cheng ; Fu, Shan

B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor-T cell (CAR-T) therapy is used for refractory or relapsed multiple myeloma (r/r MM). Concern of the safety and efficacy of CAR-T cell therapy in patients with chronic or resolved HBV infection is raised. In this study, we retrospectively reviewed 99 patients with r/r MM treated with BCMA-targeted CAR-T cell therapy, of which 7 (7.1%) patients had chronic HBV infection, 43 (43.4%) with resolved HBV infection, and the remaining 49 (49.49%) HBV-uninfected. Patients' characteristics before CAR-T cell administration were comparable in different status of HBV infection. Patients' liver function, cytokine levels, CAR-T cell expansion and cytokine release syndrome (CRS) grade after CAR-T cell therapy did not differ in different HBV serologic status. Furthermore, chronic HBV infection or resolved HBV infection did not affect clinical response, progress-free survival (PFS), or overall survival (OS). Four (4.04%) patients experienced HBV reactivation, 3 (6.98%) with resolved HBV infection, and 1 (14.29%) chronic HBV infection. Of 4 patients with HBV reactivation, 2 cases (50%) of severe hepatitis were noted and reported. Drops of serum IgG and elevation of alanine aminotransferase (ALT), alanine aminotransferase (AST), total bilirubin (TB) were observed in all four patients around the date of HBV reactivation.

100 项与 BCMA-TGFβ CAR-T cells(Medical College of Wisconsin) 相关的药物交易

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