Delving into the Latest Updates on Autologous anti-CD19 CAR-T cells expressing a shRNA against IL-6(Shanghai Unicar) with Synapse

Overview

Basic Info

Drug Type

Autologous CAR-T

Synonyms

ssCART-19, ssCART-19 cells, ssCART-19(Shanghai Unicar)

+ [1]

Target

CD19

Mechanism

CD19 inhibitors(B-lymphocyte antigen CD19 inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases

Active Indication

CD19-positive B-cell acute lymphoblastic leukemiaCD19 positive Acute Lymphoblastic LeukemiaAdult Acute Lymphocytic Leukemia+ [1]

Inactive Indication-

Originator Organization

Shanghai Unicar-Therapy Bio-medicine Technology Co., Ltd.

Active Organization

Shanghai Unicar-Therapy Bio-medicine Technology Co., Ltd.

The First Affiliated Hospital of Soochow University

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

RegulationOrphan Drug (US)

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This study is a Phase II, single-arm, open-label, non-randomized, dose-escalation clinical trial to evaluate the efficacy and safety of ssCART-19 Cell Injection in the treatment of patients with CD19 positive Relapsed or Refractory acute lymphoblastic leukemia, including central nervous system infiltration.

Start Date01 Apr 2024

Sponsor / Collaborator

Shanghai Unicar-Therapy Bio-medicine Technology Co., Ltd.

[+2]

NCT04825496 / RecruitingPhase 1

Clinical Study of ssCART-19 Cells in Patients With CD19 Positive Relapsed or Refractory Acute Lymphoblastic Leukemia

This is a single arm, open-label, non-randomized, dose-escalation, phase I study to determine the safety and efficacy of ssCART-19 in the treatment of patients with CD19 positive relapsed or refractory acute lymphoblastic leukemia.

Start Date09 Apr 2021

Sponsor / Collaborator

Shanghai Unicar-Therapy Bio-medicine Technology Co., Ltd.

[+1]

CTR20210238 / RecruitingPhase 1

具有沉默白介素6表达功能的靶向CD19基因工程化自体T细胞注射液（ssCART-19）在CD19阳性难治复发急性B淋巴细胞白血病患者中的安全性、耐受性及初步疗效的临床研究

[Translation] A clinical study on the safety, tolerability and preliminary efficacy of CD19-targeted genetically engineered autologous T cell injection (ssCART-19) with silencing interleukin-6 expression in patients with CD19-positive refractory relapsed acute B-lymphoblastic leukemia

评价具有沉默白介素6表达功能的靶向CD19基因工程化自体T细胞注射液（ssCART-19）在CD19阳性难治复发急性B淋巴细胞白血病患者中的安全性、耐受性及初步疗效。

[Translation]

To evaluate the safety, tolerability and preliminary efficacy of CD19-targeted genetically engineered autologous T cell injection (ssCART-19) with the function of silencing interleukin-6 expression in patients with CD19-positive refractory relapsed acute B-lymphoblastic leukemia.

Start Date09 Apr 2021

Sponsor / Collaborator

Shanghai Unicar-Therapy Bio-medicine Technology Co., Ltd.

100 Clinical Results associated with Autologous anti-CD19 CAR-T cells expressing a shRNA against IL-6(Shanghai Unicar)

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100 Translational Medicine associated with Autologous anti-CD19 CAR-T cells expressing a shRNA against IL-6(Shanghai Unicar)

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100 Patents (Medical) associated with Autologous anti-CD19 CAR-T cells expressing a shRNA against IL-6(Shanghai Unicar)

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255

Literatures (Medical) associated with Autologous anti-CD19 CAR-T cells expressing a shRNA against IL-6(Shanghai Unicar)

01 Oct 2024·HemaSphere

Safe and potent anti‐CD19 CAR T‐cells with shRNA‐IL‐6 gene silencing element in patients with refractory or relapsed B‐cell acute lymphoblastic leukemia

Article

Author: Tan, Jing‐Wen ; Miao, Miao ; Xu, Nan ; Yan, Jia‐Wei ; Li, Li‐Min ; Han, Yue ; Xue, Sheng‐Li ; Jia, Xu ; Dai, Hai‐Ping ; Zhu, Hong‐Jia ; Gong, Wen‐Jie ; Ma, Jin‐Feng ; Liu, Mei‐Jing ; Yu, Zhou ; Zhang, Zhi‐Zhi ; Yu, Lei ; Qiu, Hui‐Ying ; Tang, Xiao‐Wen ; Wang, Miao ; Kang, Li‐Qing ; Wu, De‐Pei ; Yan, Chun‐Long

AbstractSevere cytokine release syndrome (sCRS) and immune effector cell‐associated neurotoxicity syndrome (ICANS) have limited the widespread use of chimeric antigen receptor T (CAR T)‐cell therapy. We designed a novel anti‐CD19 CAR (ssCART‐19) with a small hairpin RNA (shRNA) element to silence the interleukin‐6 (IL‐6) gene, hypothesizing it could reduce sCRS and ICANS by alleviating monocyte activation and proinflammatory cytokine release. In a post hoc analysis of two clinical trials, we compared ssCART‐19 with common CAR T‐cells (cCART‐19) in relapsed/refractory B‐cell acute lymphoblastic leukemia (r/r B‐ALL). Among 87 patients, 47 received ssCART‐19 and 40 received cCART‐19. Grade ≥3 CRS occurred in 14.89% (7/47) of the ssCART‐19 group versus 37.5% (15/40) in the cCART‐19 group (p = 0.036). ICANS occurred in 4.26% (2/47) of the ssCART‐19 group (all grade 1) compared to 15% (2/40) of the cCART‐19 group. Patients in the ssCART‐19 group showed comparable rates of treatment response (calculated with rates of complete remission and incomplete hematological recovery) were 91.49% (43/47) for ssCART‐19 and 85% (34/40) for cCART‐19 (p = 0.999). With a median follow‐up of 21.9 months, cumulative nonrelapse mortality was 10.4% for ssCART‐19 and 13.6% for cCART‐19 (p = 0.33). Median overall survival was 37.17 months for ssCART‐19 and 32.93 months for cCART‐19 (p = 0.40). Median progression‐free survival was 24.17 months for ssCART‐19 and 9.33 months for cCART‐19 (p = 0.23). These data support the safety and efficacy of ssCART‐19 for r/r B‐ALL, suggesting its potential as a promising therapy.

15 Aug 2024·Blood

CD20-bispecific antibodies improve response to CD19-CAR T cells in lymphoma in vitro and CLL in vivo models

Article

Author: Dietrich, Sascha ; Roessner, Philipp M. ; Bruch, Peter-Martin ; Liebers, Nora ; Schmitt, Michael ; Coelho, Mariana ; Brinkmann, Berit J. ; Floerchinger, Alessia ; Schniederjohann, Christina ; Dötsch, Sarah ; Seiffert, Martina ; Mack, Norman ; Busch, Dirk H. ; Neumann, Frank ; Roider, Tobias

AbstractRelapse after anti-CD19 chimeric antigen receptor (CD19-CAR) occurs in a substantial proportion of patients with lymphoid malignancies. We assessed the potential benefits of co-administering CD20-targeting bispecific antibodies (CD20-BsAbs) with CD19-CAR T cells with the aim of enhancing immunotherapeutic efficacy. Addition of CD20-BsAbs to cocultures of CD19-CARs and primary samples of B-cell malignancies, comprising malignant B cells and endogenous T cells, significantly improved killing of malignant cells and enhanced the expansion of both endogenous T cells and CD19-CAR T cells. In an immunocompetent mouse model of chronic lymphocytic leukemia, relapse after initial treatment response frequently occurred after CD19-CAR T-cell monotherapy. Additional treatment with CD20-BsAbs significantly enhanced the treatment response and led to improved eradication of malignant cells. Higher efficacy was accompanied by improved T-cell expansion with CD20-BsAb administration and led to longer survival with 80% of the mice being cured with no detectable malignant cell population within 8 weeks of therapy initiation. Collectively, our in vitro and in vivo data demonstrate enhanced therapeutic efficacy of CD19-CAR T cells when combined with CD20-BsAbs in B-cell malignancies. Activation and proliferation of both infused CAR T cells and endogenous T cells may contribute to improved disease control.

01 Aug 2024·Molecular Therapy

Bispecific antibodies and autologous chimeric antigen receptor T cell therapies for treatment of hematological malignancies

Review

Author: Al Hadidi, Samer ; Brenner, Malcolm K ; Suzuki, Masataka ; Heslop, Helen E

In recent years, the therapeutic landscape for hematological malignancies has markedly advanced, particularly since the inaugural approval of autologous chimeric antigen receptor T cell (CAR-T) therapy in 2017 for relapsed/refractory acute lymphoblastic leukemia (ALL). Autologous CAR-T therapy involves the genetic modification of a patient's T cells to specifically identify and attack cancer cells, while bispecific antibodies (BsAbs) function by binding to both cancer cells and immune cells simultaneously, thereby triggering an immune response against the tumor. The subsequent approval of various CAR-T therapies and BsAbs have revolutionized the treatment of multiple hematological malignancies, highlighting high response rates and a subset of patients achieving prolonged disease control. This review explores the mechanisms underlying autologous CAR-T therapies and BsAbs, focusing on their clinical application in multiple myeloma, ALL, and non-Hodgkin lymphoma. We provide comprehensive insights into their individual efficacy, limitations concerning broad application, and the potential of combination therapies. These upcoming strategies aim to propel the field forward, paving the way for safer and more effective therapeutic interventions in hematological malignancies.

100 Deals associated with Autologous anti-CD19 CAR-T cells expressing a shRNA against IL-6(Shanghai Unicar)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
CD19-positive B-cell acute lymphoblastic leukemia	Phase 2	CN	Shanghai Unicar-Therapy Bio-medicine Technology Co., Ltd.	08 Apr 2024
CD19 positive Acute Lymphoblastic Leukemia	Phase 2	CN	Shanghai Unicar-Therapy Bio-medicine Technology Co., Ltd.	01 Apr 2024
CD19 positive Acute Lymphoblastic Leukemia	Phase 2	CN	The First Affiliated Hospital of Soochow University	01 Apr 2024
Adult Acute Lymphocytic Leukemia	Phase 2	CN	The First Affiliated Hospital of Soochow University	01 Jan 2018
Refractory Adult Acute Lymphoblastic Leukemia	Phase 1	CN	Shanghai Unicar-Therapy Bio-medicine Technology Co., Ltd.	09 Apr 2021

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04825496 (ESMO2024) Manual	Phase 1	Pre B-cell acute lymphoblastic leukemia	17	ssCART-19	(ygwlxxsfyj) = lymphopenia (94.2%), transient neutropenia (88.2%), leukopenia (88.2%), anaemia (70.6%) and thrombocytopenia (58.8%). grtknwzepv (yhybnyxpkv ) View more	Positive	13 Sep 2024
NCT04825496 (ssCART-19, ASH2023)	Phase 1	Refractory B Acute Lymphoblastic Leukemia	13	ssCART-19	(nwysrmpdwl) = 9 patients (75.0%) developed CRS, and 3 patients (25.0%) were grade 3 CRS dfemkpqeya (ehcjtwpwtw ) View more	-	10 Dec 2023