Improving CAR T cell immunotherapy–mediated remissions for pediatric leukemia

Barrett, David M.

doi:10.1172/jci128743

Cited by 7 publications

(6 citation statements)

References 17 publications

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“…The PFS rates at 12 months were 77.1%, 63.5%, 43.5%, and 0% in the DS 1-2, DS3, DS4 and DS5 groups, respectively, and the OS rates were 87.1%, 86.2%, 61.7%, and 38.1%, respectively ( 84 ). Circulating tumor DNA (ctDNA) has become a marker for risk stratification and a predictor of the efficacy of chemotherapy in DLBCL patients ( 85 – 88 ), and preliminary data indicated that molecular remission determined based on ctDNA monitoring successfully predicted the outcomes ( 74 , 88 ). Further study conducted by Matthew and colleagues frequently monitored ctDNA in LBCL patients treated with Axi-cel from the initiation of the lymphodepleting process to 1 year following CAR-T infusion or disease progression ( 88 ).…”

Section: Biomarkers For Long-term Efficacymentioning

confidence: 99%

Predictive short/long-term efficacy biomarkers and resistance mechanisms of CD19-directed CAR-T immunotherapy in relapsed/refractory B-cell lymphomas

Wang

et al. 2023

Front. Immunol.

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Genetically modified T-cell immunotherapies are revolutionizing the therapeutic options for hematological malignancies, especially those of B-cell origin. Impressive efficacies of CD19-directed chimeric antigen receptor (CAR)-T therapy have been reported in refractory/relapsed (R/R) B-cell non-Hodgkin lymphoma (NHL) patients who were resistant to current standard therapies, with a complete remission (CR) rate of approximately 50%. At the same time, problems of resistance and relapse following CAR-T therapy have drawn growing attention. Recently, great efforts have been made to determine various factors that are connected to the responses and outcomes following CAR-T therapy, which may not only allow us to recognize those with a higher likelihood of responding and who could benefit most from the therapy but also identify those with a high risk of resistance and relapse and to whom further appropriate treatment should be administered following CAR-T therapy. Thus, we concentrate on the biomarkers that can predict responses and outcomes after CD19-directed CAR-T immunotherapy. Furthermore, the mechanisms that may lead to treatment failure are also discussed in this review.

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Section: Biomarkers For Long-term Efficacymentioning

confidence: 99%

Predictive short/long-term efficacy biomarkers and resistance mechanisms of CD19-directed CAR-T immunotherapy in relapsed/refractory B-cell lymphomas

Wang

et al. 2023

Front. Immunol.

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“…T-cell intrinsic-related factors include the proportion of CD4:CD8 T cells, T-cell differentiation, the expression of exhaustion markers, and the T-cell metabolic profile [117]. Several reports have suggested that the CD4:CD8 T-cell ratio is not associated with the efficacy (response and survival rates) and safety (grade ≥3 CRS or neurological events (NE)) of CAR-T-cell therapy (Tisa-cel and Axi-cel) for patients with DLBCL [9].…”

Section: Timely Leukapheresis and Cryopreservationmentioning

confidence: 99%

The Past, Present, and Future of Clinically Applied Chimeric Antigen Receptor-T-Cell Therapy

et al. 2022

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Immunotherapy represents the fourth pillar of cancer therapy after surgery, chemotherapy, and radiation. Chimeric antigen receptor (CAR)-T-cell therapy is an artificial immune cell therapy applied in clinical practice and is currently indicated for hematological malignancies, with cluster of differentiation 19 (CD19) as its target molecule. In this review, we discuss the past, present, and future of CAR-T-cell therapy. First, we summarize the various clinical trials that were conducted before the clinical application of CD19-targeted CAR-T-cell therapies began. Second, we discuss the accumulated real-world evidence and the barriers associated with applying clinical trials to clinical practices from the perspective of the quality and technical aspects. After providing an overview of all the moving parts involved in the production of CAR-T-cell products, we discuss the characteristics of immune cells (given that T cells are the raw materials for CAR-T-cell therapy) and elucidate the relationship between lifestyle, including diet and exercise, and immune cells. Finally, we briefly highlight future trends in the development of immune cell therapy. These advancements may help position CAR-T-cell therapy as a standard of care.

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“…Hu et al developed an IL-18expressing CD19 CAR-T cell product that exhibited enhanced proliferation and anti-tumor ability in a mouse model (56). CAR activity, is associated with prolonged remission after CAR-T cell treatment (59). Finney et al treated 43 pediatric and adult RR-ALL patients with CD19 CAR-T cell therapy and demonstrated that the ongoing persistence of functional CD19 CAR-T cells or BCA for more than 6 months was a major determinant of durable remission, which was positively correlated with CD19 antigen burden at the time of infusion (46).…”

Section: Biomarkers For Immune Checkpointsmentioning

confidence: 99%

“…Meanwhile, CD19 CAR-T cells can target all CD19-positive B cells and causes BCA of flexible duration. Hence, BCA usually act as a marker of in vivo CAR activity, is associated with prolonged remission after CAR-T cell treatment ( 59 ). Finney et al.…”

Section: Biomarkers For Therapeutic Response In Car-t Cell Therapymentioning

confidence: 99%

Biomarkers for Chimeric Antigen Receptor T Cell Therapy in Acute Lymphoblastic Leukemia: Prospects for Personalized Management and Prognostic Prediction

Hong

Huang

2021

Front. Immunol.

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Chimeric antigen receptor (CAR) T cell therapy represents a breakthrough in immunotherapy with the potential of ushering in a new era in cancer treatment. Remarkable therapeutic response and complete remission of this innovative management have been observed in patients with relapse/refractory acute lymphoblastic leukemia. With CAR-T cell therapy becoming widely used both in multicenter clinical trials and as a commercial treatment, therapeutic efficacy monitoring and management of toxicities will be indispensable for ensuring safety and improving overall survival. Biomarkers can act not only as effective indicators reflecting patients’ baseline characteristics, CAR-T cell potency, and the immune microenvironment, but can also assess side effects during treatment. In this review, we will elaborate on a series of biomarkers associated with therapeutic response as well as treatment-related toxicities, and present their current condition and latent value with respect to the clinical utility. The combination of biomarker research and CAR-T cell therapy will contribute to establishing a safer and more powerful monitoring system and prolonging the event-free survival of patients.

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Improving CAR T cell immunotherapy–mediated remissions for pediatric leukemia

Cited by 7 publications

References 17 publications

Predictive short/long-term efficacy biomarkers and resistance mechanisms of CD19-directed CAR-T immunotherapy in relapsed/refractory B-cell lymphomas

Predictive short/long-term efficacy biomarkers and resistance mechanisms of CD19-directed CAR-T immunotherapy in relapsed/refractory B-cell lymphomas

The Past, Present, and Future of Clinically Applied Chimeric Antigen Receptor-T-Cell Therapy

Biomarkers for Chimeric Antigen Receptor T Cell Therapy in Acute Lymphoblastic Leukemia: Prospects for Personalized Management and Prognostic Prediction

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