Delving into the Latest Updates on Anti CD22 CAR-T cell therapy (Hebei Senlang Biotechnology) with Synapse

Overview

Basic Info

Drug Type

CAR-T

Synonyms

Anti CD22 CART cell Hebei Senlang Biotechnology, CD22 CART Hebei Senlang Biotechnology

Target

CD22

Action

inhibitors

Mechanism

CD22 inhibitors(CD22 inhibitors), Gene transference, T lymphocyte replacements

Therapeutic Areas

Immune System DiseasesHemic and Lymphatic Diseases

Active Indication

B-Cell Malignant Neoplasm

Inactive Indication

Acute Lymphoblastic LeukemiaNon-Hodgkin LymphomaNon-Hodgkin's lymphoma refractory+ [4]

Originator Organization

Hebei Senlangbio Biotechnology Co., Ltd.

Active Organization

Hebei Senlangbio Biotechnology Co., Ltd.

Inactive Organization-

License Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 133477linker

Sequence Code 71180linker

Sequence Code 524515405

Sequence Code 524515406

Sequence Code 524515404

Sequence Code 524515407ScFv

Author: Taylor, Naomi ; Hinrichs, Christian S. ; Rae, Zachary ; Draper, Lindsey M. ; Kelly, Michael C. ; Ishii, Kazusa ; Achar, Sooraj R. ; Zhang, Ling ; Norberg, Scott M. ; Nguyen, Kilyna A. ; Liu, Zhihui ; Davies, John S. ; Altan-Bonnet, Gregoire ; Meyer, Thomas J. ; McIntosh, Crystal P. ; Wu, Xiaolin

Chimeric antigen receptor (CAR) T cells effectively treat B cell malignancies. However, CAR-T cells cause inflammatory toxicities such as cytokine release syndrome (CRS), which is in contrast to T cell receptor (TCR)–engineered T cells against various antigens that historically have rarely been associated with CRS. To study whether and how differences in receptor types affect the propensity for eliciting inflammatory responses in a model system wherein TCR and CAR target equalized sources of clinically relevant antigen, we discovered a CD22-specific TCR and compared it to CD22 CAR. Both CD22 TCR-T and CD22 CAR-T cells eradicated leukemia in xenografts, but only CD22 CAR-T cells induced dose-dependent systemic inflammation. Compared to TCR-T cells, CAR-T cells disproportionately upregulated inflammatory pathways without concordant augmentation in pathways involved in direct cytotoxicity upon antigen engagement. These differences in antileukemia responses comparing TCR-T and CAR-T cells highlight the potential opportunity to improve therapeutic safety by using TCRs.

01 Aug 2024·Acta Pharmaceutica Sinica B

Unlocking T cell exhaustion: Insights and implications for CAR-T cell therapy

Review

Author: Yu, Haijun ; Sun, Zhi-Jun ; Xiong, Dian

Chimeric antigen receptor T (CAR-T) cell therapy as a form of adoptive cell therapy (ACT) has shown significant promise in cancer treatment, demonstrated by the FDA-approved CAR-T cell therapies targeting CD19 or B cell maturation antigen (BCMA) for hematological malignancies, albeit with moderate outcomes in solid tumors. However, despite these advancements, the efficacy of CAR-T therapy is often compromised by T cell exhaustion, a phenomenon that impedes the persistence and effector function of CAR-T cells, leading to a relapse rate of up to 75% in patients treated with CD19 or CD22 CAR-T cells for hematological malignancies. Strategies to overcome CAR-T exhaustion employ state-of-the-art genomic engineering tools and single-cell sequencing technologies. In this review, we provide a comprehensive understanding of the latest mechanistic insights into T cell exhaustion and their implications for the current efforts to optimize CAR-T cell therapy. These insights, combined with lessons learned from benchmarking CAR-T based products in recent clinical trials, aim to address the challenges posed by T cell exhaustion, potentially setting the stage for the development of tailored next-generation approaches to cancer treatment.

22 Mar 2023·Journal of translational medicine

Safety and efficacy of co-administration of CD19 and CD22 CAR-T cells in children with B-ALL relapse after CD19 CAR-T therapy.

Article

Author: Shi, Wenhua ; Ding, Lixia ; Song, Lili ; Li, Benshang ; Yang, Jing ; Wan, Xinyu ; Wang, Xiang ; Gu, Longjun ; Lu, Jun ; Tang, Yanjing ; Chen, Jing ; Luo, Chengjuan ; Yang, Xiaomin ; Ma, Yani ; Li, Wenjie ; Wang, Tianyi ; Tang, Jingyan

BACKGROUNDCD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy has shown remarkable efficacy in treating relapsed or refractory pediatric B-lineage acute lymphoblastic leukemia (B-ALL). However, poor results are obtained when the same product is reused in patients who relapse after CAR-T. Therefore, there is a need to explore the safety and efficacy of co-administration of CD19- and CD22-targeted CAR-T as a salvage second CAR-T therapy (CART2) in B-ALL patients who relapse after their first CD19 CAR-T treatment (CART1).METHODSIn this study, we recruited five patients who relapsed after CD19-targeted CAR-T. CD19- and CD22-CAR lentivirus-transfected T cells were cultured separately and mixed before infusion in an approximate ratio of 1:1. The total dose range of CD19 and CD22 CAR-T was 4.3 × 10⁶-1.5 × 10⁷/kg. Throughout the trial, we evaluated the patients' clinical responses, side effects, and the expansion and persistence of CAR-T cells.RESULTSAfter CART2, all five patients had minimal residual disease (MRD)-negative complete remission (CR). The 6- and 12-month overall survival (OS) rates were 100%. The median follow-up time was 26.3 months. Three of the five patients bridged to consolidated allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CART2 and remained in MRD-negative CR at the cut-off time. In patient No. 3 (pt03), CAR-T cells were still detected in the peripheral blood (PB) at 347 days post-CART2. Cytokine release syndrome (CRS) only occurred with a grade of ≤ 2, and no patients experienced symptoms of neurologic toxicity during CART2.CONCLUSIONSMixed infusion of CD19- and CD22-targeted CAR-T cells is a safe and effective regimen for children with B-ALL who relapse after prior CD19-targeted CAR-T therapy. Salvage CART2 provides an opportunity for bridging to transplantation and long-term survival.TRIAL REGISTRATIONChinese Clinical Trial Registry, ChiCTR2000032211. Retrospectively registered: April 23, 2020.

100 Deals associated with Anti CD22 CAR-T cell therapy (Hebei Senlang Biotechnology)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
B-Cell Malignant Neoplasm	Phase 1	China	Hebei Senlangbio Biotechnology Co., Ltd.	08 Apr 2022
Non-Hodgkin's lymphoma refractory	Discovery	China	Hebei Senlangbio Biotechnology Co., Ltd.	01 Apr 2020
Pre B-cell acute lymphoblastic leukemia	Discovery	China	Hebei Senlangbio Biotechnology Co., Ltd.	01 Apr 2020
Recurrent Adult Acute Lymphoblastic Leukemia	Discovery	China	Hebei Senlangbio Biotechnology Co., Ltd.	01 Apr 2020
refractory acute lymphoid leukemia in relapse	Discovery	China	Hebei Senlangbio Biotechnology Co., Ltd.	01 Apr 2020
Refractory Indolent Adult Non-Hodgkin Lymphoma	Discovery	China	Hebei Senlangbio Biotechnology Co., Ltd.	01 Apr 2020
Acute Lymphoblastic Leukemia	Discovery	China	Hebei Senlangbio Biotechnology Co., Ltd.	26 Mar 2020
Non-Hodgkin Lymphoma	Discovery	China	Hebei Senlangbio Biotechnology Co., Ltd.	11 Mar 2020

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASH2023	Phase 2	Philadelphia positive acute lymphocytic leukaemia First line	18	Dasatinib + CD19 CAR-T cell therapy	(ieqkwbxzfz) = jegdlwsude fqycvvrhcm (idljrpzair )	Positive	11 Dec 2023
				Dasatinib + CD22 CAR-T cell therapy	(ieqkwbxzfz) = pmdwdgoovh fqycvvrhcm (idljrpzair )