A novel antibody-TCR (AbTCR) T-cell therapy is safe and effective against CD19-positive relapsed/refractory B-cell lymphoma

He, Pengcheng; Li, Haibo; Zimdahl, Bryan; Wang, Jie; Luo, Minna; Chang, Qi; Tian, Fangzhou; Fan, Ni; Yu, Duo; Liu, Huasheng; Chen, Limei; Wang, Huaiyu; Zhang, Mei; Grupp, Stephan A.; Liu, Cheng

doi:10.1007/s00432-022-04132-9

Cited by 5 publications

(4 citation statements)

References 33 publications

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“…Of these 138 patients, 49 and 89 patients suffered from hematological and solid cancers, respectively. Nine hematological malignancies were 2) (84). For solid tumors, there were 12 kinds of cancers recorded, with 10 cancers in female patients (n = 38) (Figure 4B, left panels) and seven cancers in male patients (n = 51) (Figure 4B, right panels).…”

Section: Current Gd T-cell Immunotherapy Clinical Resultsmentioning

confidence: 98%

“…In addition to the previously mentioned strategies aimed at utilizing the inherent anticancer capabilities of Vg9Vd2 T cells, there have been recent human trials investigating gd Tcell-related T-cell modifications. These modification techniques include the addition of a chimeric antigen receptor (CAR) to gd T cells to create CAR-gd T cells; the transfer of antitumor gd TCR to ab T cells (TEG001, GDT002, GDT201); the fusion of an antibody anti-CD19 Fab region and the transmembrane andendo domains of a gd TCR, as well as a separate CD19 single-chain variable fragment (scFv) and a 4-1BB costimulatory molecule, to create a novel T cell (ET019003) to treat B-cell lymphoma (84).…”

Section: Current Strategies In Practicementioning

confidence: 99%

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A close look at current γδ T-cell immunotherapy

Yang

Zhou

2023

Front. Immunol.

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Owing to their antitumor and major histocompatibility complex (MHC)-independent capacities, γδ T cells have gained popularity in adoptive T-cell immunotherapy in recent years. However, many unknowns still exist regarding γδ T cells, and few clinical data have been collected. Therefore, this review aims to describe all the main features of the applications of γδ T cells and provide a systematic view of current γδ T-cell immunotherapy. Specifically, this review will focus on how γδ T cells performed in treating cancers in clinics, on the γδ T-cell clinical trials that have been conducted to date, and the role of γδ T cells in the pharmaceutical industry.

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Section: Current Gd T-cell Immunotherapy Clinical Resultsmentioning

confidence: 98%

Section: Current Strategies In Practicementioning

confidence: 99%

A close look at current γδ T-cell immunotherapy

Yang

Zhou

2023

Front. Immunol.

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“…Upcoming trials will help to determine if this highly precise gene editing would translate into improved clinical outcomes. To mitigate CAR T exhaustion, a novel platform has been investigated in autologous CAR Ts for lymphoma, involving γδ TCR coupled with a costimulatory agent as an alternative to CAR ( 47 ). While this approach has not yet been explored in allogeneic T-cell therapies, it could potentially reduce GVHD risk and increase effectiveness of alloCAR Ts.…”

Section: Limitations Of Allocar Ts and Future Perspectivesmentioning

confidence: 99%

“Off-The-Shelf” allogeneic chimeric antigen receptor T-cell therapy for B-cell malignancies: current clinical evidence and challenges

Mohty,

Lazaryan

2024

Front. Oncol.

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Chimeric antigen receptor T-cell therapy (CAR T) has revolutionized the treatment landscape for hematologic malignancies, notably B-cell non-Hodgkin lymphoma (B-NHL) and B-cell acute lymphoblastic leukemia (B-ALL). While autologous CAR T products have shown remarkable efficacy, their complex logistics, lengthy manufacturing process, and high costs impede widespread accessibility and pose therapeutic challenge especially for patients in rapid need for therapy. “Off-the-shelf” allogeneic CAR T-cell therapy (alloCAR T) has emerged as a promising alternative therapy, albeit experimental to date. AlloCARTs are derived from healthy donors, manufactured by batches and stored, making them available off-the-shelf which lowers financial burden. Various gene editing techniques have been employed to mitigate graft-versus-host disease (GVHD) and host-versus-graft (HvG) to enhance alloCAR T persistence. In this review, we summarize available manufacturing techniques, current evidence, and discuss challenges faced with the use of alloCAR Ts.

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“…102 Hybrid approaches, such as TCRm gives CAR cell therapies the ability to access intracellular antigens. 111 AbTCR is another hybrid approach that gives TCRs typical antibody recognition 214,215 and are currently being studied further (Figure 3).…”

Section: Protec Ting Cell S From Hos T At Tackmentioning

confidence: 99%

Challenges and solutions for therapeuticTCR‐based agents

Malviya

Aretz

Molvi

et al. 2023

Immunological Reviews

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SummaryRecent development of methods to discover and engineer therapeutic T‐cell receptors (TCRs) or antibody mimics of TCRs, and to understand their immunology and pharmacology, lag two decades behind therapeutic antibodies. Yet we have every expectation that TCR‐based agents will be similarly important contributors to the treatment of a variety of medical conditions, especially cancers. TCR engineered cells, soluble TCRs and their derivatives, TCR‐mimic antibodies, and TCR‐based CAR T cells promise the possibility of highly specific drugs that can expand the scope of immunologic agents to recognize intracellular targets, including mutated proteins and undruggable transcription factors, not accessible by traditional antibodies. Hurdles exist regarding discovery, specificity, pharmacokinetics, and best modality of use that will need to be overcome before the full potential of TCR‐based agents is achieved. HLA restriction may limit each agent to patient subpopulations and off‐target reactivities remain important barriers to widespread development and use of these new agents. In this review we discuss the unique opportunities for these new classes of drugs, describe their unique antigenic targets, compare them to traditional antibody therapeutics and CAR T cells, and review the various obstacles that must be overcome before full application of these drugs can be realized.

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A novel antibody-TCR (AbTCR) T-cell therapy is safe and effective against CD19-positive relapsed/refractory B-cell lymphoma

Cited by 5 publications

References 33 publications

A close look at current γδ T-cell immunotherapy

A close look at current γδ T-cell immunotherapy

“Off-The-Shelf” allogeneic chimeric antigen receptor T-cell therapy for B-cell malignancies: current clinical evidence and challenges

Challenges and solutions for therapeuticTCR‐based agents

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