The CD4/CD8 ratio of infused CD19-CAR-T is a prognostic factor for efficacy and toxicity

Article Hematology

Costimulatory domains direct distinct fates of CAR-driven T-cell dysfunction

Mehmet Emrah Selli et al.

Summary: In this study, an in vitro model was developed to induce T-cell dysfunction through chronic CAR activation, and the impact of CAR costimulatory domains on T-cell failure was investigated. The study found that chronic activation of CD28-based CARs resulted in T-cell exhaustion and dysfunction. In contrast, 41BB-based CARs activated a different molecular program and led to the differentiation of T cells into a novel cell state.

BLOOD (2023)

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Review Hematology

Mechanisms of Resistance and Treatment of Relapse after CAR T-cell Therapy for Large B-cell Lymphoma and Multiple Myeloma

Kai Rejeski et al.

Summary: CAR-T cell therapy has revolutionized the treatment of relapsed/refractory B cell malignancies and multiple myeloma, but long-term disease remission is achieved in only a small percentage of patients. Resistance to CAR-T can be attributed to various factors, including host-related, tumor-intrinsic, microenvironmental, macroenvironmental, and CAR-T-related factors. Understanding these resistance mechanisms can guide the development of strategies to overcome resistance to CAR-T.

TRANSPLANTATION AND CELLULAR THERAPY (2023)

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Article Oncology

Phenotypic Composition of Commercial Anti-CD19 CAR T Cells Affects In Vivo Expansion and Disease Response in Patients with Large B-cell Lymphoma

Chiara Monfrini et al.

Summary: This study found that the in vivo expansion of CAR T cells is associated with therapeutic efficacy. Additionally, the content and characteristics of CAR T bag cells have a significant impact on in vivo expansion, treatment response, and survival.

CLINICAL CANCER RESEARCH (2022)

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Letter Hematology

Real-world characteristics of T-cell apheresis and clinical response to tisagenlecleucel in B-cell lymphoma

Alexis Cuffel et al.

BLOOD ADVANCES (2022)

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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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Article Oncology

Clinical and Product Features Associated with Outcome of DLBCL Patients to CD19-Targeted CAR T-Cell Therapy

Sylvain Lamure et al.

Summary: In this study of 60 patients with relapsed/refractory diffuse large B-cell lymphoma and transformed follicular lymphoma who received CD19-directed CAR T-cell therapy, a complete metabolic response was achieved in 40% of patients, with a partial metabolic response in 23%. Factors such as age-adjusted international prognostic index, product features, in vivo expansion, and CAR T-cell exhaustion phenotype were significantly associated with the efficacy of the therapy.

CANCERS (2021)

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Review Oncology

Recent advances and discoveries in the mechanisms and functions of CAR T cells

Rebecca C. Larson et al.

Summary: This review summarizes the major advances that have been made in the efficacy and safety of CAR T cell therapies over the past 3 years and looks ahead to new findings that will impact the future of this immunotherapy.

NATURE REVIEWS CANCER (2021)

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Article Hematology