Killer fatigue: Transition to NK-cell-like phenotype is a signature of CAR-T cell exhaustion

Article Biochemistry & Molecular Biology

An NK-like CAR T cell transition in CAR T cell dysfunction

Charly R. Good et al.

Summary: CAR T cell therapy has achieved success in hematological malignancies but faces challenges in solid tumors due to CAR T cell exhaustion. Dysfunction of CAR T cells in solid tumors is associated with CD8+ T-to-NK-like T cell transition, and genetic downregulation of ID3 and SOX4 expression can improve the efficacy of CAR T cell therapy.

CELL (2021)

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Review Biotechnology & Applied Microbiology

T Cell Exhaustion and CAR-T Immunotherapy in Hematological Malignancies

Lu Tang et al.

Summary: T cell exhaustion plays an immunosuppressive role in malignant diseases, and strategies aimed at preventing or reversing it can reduce cancer morbidity and enhance immunotherapy effectiveness. Novel technologies hold promise for reversing T cell exhaustion and developing personalized strategies to restore anti-tumor immunity.

BIOMED RESEARCH INTERNATIONAL (2021)

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Review Biotechnology & Applied Microbiology

Navigating CAR-T cells through the solid-tumour microenvironment

Andrew J. Hou et al.

Summary: CAR-T cells have limited efficacy in treating solid tumors, but various engineering strategies can overcome the obstacles posed by the tumor microenvironment, producing next-generation T cells with enhanced specificity and sustained effector function.

NATURE REVIEWS DRUG DISCOVERY (2021)

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Article Multidisciplinary Sciences

Transient rest restores functionality in exhausted CAR-T cells through epigenetic remodeling

Evan W. Weber et al.

Summary: This study showed that transient cessation of chimeric antigen receptor (CAR) signaling can enhance the efficacy of CAR-T cells, reactivating their anti-tumor functions, and challenging the notion that exhaustion is an epigenetically fixed state.

SCIENCE (2021)

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Review Hematology

Efficacy and safety of CD19-directed CAR-T cell therapies in patients with relapsed/refractory aggressive B-cell lymphomas: Observations from the JULIET, ZUMA-1, and TRANSCEND trials

Jason R. Westin et al.

Summary: CAR-T cell therapies have improved outcomes for patients with relapsed or refractory aggressive B-cell lymphomas. Despite similarities in CAR technologies, there are differences in manufacturing, clinical trial designs, and data reporting among CAR-T cell products. Real-world use of axicabtagene ciloleucel and tisagenlecleucel will help validate the impact of patient characteristics on efficacy and safety. Monitoring patients for sustained responses and potential long-term side effects post CAR-T cell therapy will be crucial.

AMERICAN JOURNAL OF HEMATOLOGY (2021)

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Review Oncology