DAP10 integration in CAR-T cells enhances the killing of heterogeneous tumors by harnessing endogenous NKG2D

Li, Shanglin; Zhao, Ruocong; Zheng, Di‐Wei; Qin, Le; Cui, Yuanbin; Li, Yao; Jiang, Zhiwu; Zhong, Mengjun; Shi, Jie; Li, Ming; Wang, Xindong; Tang, Zhaoyang; Wu, Qianni; Long, Youguo; Duo, Hu; Wang, Suna; Yao, Yao; Liu, Shuang; Yang, Li-Hua; Zhang, Zhenfeng; Tang, Qingli; Li, Yangqiu; Li, Peng

doi:10.1016/j.omto.2022.06.003

Cited by 10 publications

(5 citation statements)

References 32 publications

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“…Although all strategies effectively eliminated tumor cells and resulted in long-term survival, the bicistronic CARs and coadministration approaches exhibited superior efficacy. Similar preclinical results have been observed in solid tumors with dual targeting of various antigen pairs, some demonstrating limited immune evasion and persistent T cells with limited exhaustion ( 45 , 48 – 50 ). Finally, efficient targeting of three different antigens was demonstrated in several preclinical models ( 46 , 51 , 52 ).…”

Section: Vδ2 T Cells An Ideal Immune Effector For Cancer Immunotherapysupporting

confidence: 71%

“…Numerous studies have reported that BTN3A1, along with various NKG2D ligands, are commonly expressed in cancer ( 11 , 34 , 67 , 68 ). The importance of the NKG2D pathway in tumor immunosurveillance has been demonstrated through preclinical and clinical studies involving conventional NKG2D-CAR-T cells ( 50 , 69 , 70 ). These cells can migrate to tumor sites, extending the survival of tumor-bearing mice and providing protection against tumor rechallenge ( 71 ).…”

Section: Vδ2 T Cells An Ideal Immune Effector For Cancer Immunotherapymentioning

confidence: 99%

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Arming Vδ2 T Cells with Chimeric Antigen Receptors to Combat Cancer

Thomas,

Paris,

Pecqueur

2024

Clinical Cancer Research

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Immunotherapy has emerged as a promising approach in the field of cancer treatment, with chimeric antigen receptor (CAR) T cell therapy demonstrating remarkable success. However, challenges such as tumor antigen heterogeneity, immune evasion, and limited persistence of CAR-T cells have prompted the exploration of alternative cell types for CAR-based strategies. Gamma delta T cells, a unique subset of lymphocytes with inherent tumor recognition capabilities and versatile immune functions, have garnered increasing attention in recent years. In this review, we will present how arming Vδ2-T cells might be the basis for next-generation immunotherapies against solid tumors. Following a comprehensive overview of γδ T cell biology and innovative CAR engineering strategies, we will discuss the clinical potential of Vδ2 CAR-T cells to overcome the current limitations of immunotherapy in solid tumors. Indeed, while applications of Vδ2 CAR-T cells in cancer research are relatively in their infancy and many challenges are yet to be identified, Vδ2 CAR-T cells represent a promising breakthrough in cancer immunotherapy.

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Section: Vδ2 T Cells An Ideal Immune Effector For Cancer Immunotherapysupporting

confidence: 71%

Section: Vδ2 T Cells An Ideal Immune Effector For Cancer Immunotherapymentioning

confidence: 99%

Arming Vδ2 T Cells with Chimeric Antigen Receptors to Combat Cancer

Thomas,

Paris,

Pecqueur

2024

Clinical Cancer Research

View full text Add to dashboard Cite

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“…This system incorporates GPC3 single-stranded variable fragments (scFv) to create a dual-antigen targeting system. The GPC3-DAP10 CAR demonstrated remarkable efficacy in eliminating heterogeneous cancer cells in vitro and in vivo [47]. This innovative dual-targeting system enhances T-cell killing capacity against cancer cells and broadens the spectrum of tumors that can be recognized, presenting a promising strategy for the clinical treatment of glioblastoma.…”

Section: Targeting Multiple Antigensmentioning

confidence: 99%

Chimeric Antigen Receptor T-Cell Therapy for Glioblastoma

Ma,

2023

Cancers

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Glioblastoma (GBM), the most common primary brain tumor in adults, is characterized by low survival rates and a grim prognosis. Current treatment modalities, including extensive surgical resection, chemotherapy, and radiation therapy, often yield limited success due to the brain’s sensitivity, leading to significant side effects. Exciting advancements in immunotherapy have recently shown promise in treating various types of tumors, raising hopes for improved outcomes in brain tumor patients. One promising immunotherapy approach is chimeric antigen receptor (CAR) T-cell therapy, which recognizes surface proteins on targeted tumor cells and redirects cytotoxicity towards specific targets. This review aims to discuss the existing research and future prospects for CAR T-cell immunotherapy in treating glioblastoma.

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“…They tandemly incorporated it with anti-glypican 3 (GPC3) scFv to construct a dual-antigen-targeting system. This novel dual-targeting system enabled high efficacy in killing heterogeneous cancer tumors [ 70 ]. Bob S. Carter et al designed EGFRvIII and BiTE bicistronic construct CAR T cells against EGFR to solve heterogeneous target antigen expression.…”

Section: Strategies For Overcoming the Challenges Of Taasmentioning

confidence: 99%

Current advances and challenges in CAR T-Cell therapy for solid tumors: tumor-associated antigens and the tumor microenvironment

2023

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The past decade has witnessed ongoing progress in immune therapy to ameliorate human health. As an emerging technique, chimeric antigen receptor (CAR) T-cell therapy has the advantages of specific killing of cancer cells, a high remission rate of cancer-induced symptoms, rapid tumor eradication, and long-lasting tumor immunity, opening a new window for tumor treatment. However, challenges remain in CAR T-cell therapy for solid tumors due to target diversity, tumor heterogeneity, and the complex microenvironment. In this review, we have outlined the development of the CAR T-cell technique, summarized the current advances in tumor-associated antigens (TAAs), and highlighted the importance of tumor-specific antigens (TSAs) or neoantigens for solid tumors. We also addressed the challenge of the TAA binding domain in CARs to overcome off-tumor toxicity. Moreover, we illustrated the dominant tumor microenvironment (TME)-induced challenges and new strategies based on TME-associated antigens (TMAs) for solid tumor CAR T-cell therapy.

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DAP10 integration in CAR-T cells enhances the killing of heterogeneous tumors by harnessing endogenous NKG2D

Cited by 10 publications

References 32 publications

Arming Vδ2 T Cells with Chimeric Antigen Receptors to Combat Cancer

Arming Vδ2 T Cells with Chimeric Antigen Receptors to Combat Cancer

Chimeric Antigen Receptor T-Cell Therapy for Glioblastoma

Current advances and challenges in CAR T-Cell therapy for solid tumors: tumor-associated antigens and the tumor microenvironment

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