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Peripheral eosinophil counts predict efficacy of anti-CD19 CAR-T cell therapy against B-lineage non-Hodgkin lymphoma.

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机构: [1]Department of Oncology, Xinqiao Hospital, Army Medical University, Chongqing 400037, China. [2]Chongqing Key Laboratory of Immunotherapy, Chongqing 400037, China. [3]Department of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu 610041, China. [4]Department of Immunology, Duke University Medical Center, Durham, NC, USA. [5]R&D Department, HRAIN Biotechnology Co. Ltd., Shanghai, China. [6]Department of Oncology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China. [7]Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China. [8]Department of Bio-therapeutic, The First Medical Center, Chinese PLA General Hospital, Beijing, China. [9]Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA [10]Department of Pharmaceutical Sciences and Pharmacology, University of Southern California, 3710 McClintock Ave., RTH506, Los Angeles, CA 90089, USA.
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关键词: biomarker B-NHL CAR-T eosinophil infiltration

摘要:
Rationale: The onset of cytokine release syndrome (CRS) and in vivo persistence of anti-CD19 chimeric antigen receptor T (CAR-T) cells after infusion correlate with clinical responsiveness. However, there are no known baseline biomarkers that can predict the prognosis of patients with B-lineage non-Hodgkin lymphoma (B-NHL). The aim of this study was to identify blood cell populations associated with beneficial outcomes in B-NHL patients administered CAR-T cell immunotherapies. Methods: We enumerated peripheral blood and CAR-T cells by retrospectively analyzing three CAR-T cell trials involving 65 B-NHL patients. We used a preclinical model to elucidate the eosinophil mechanism in CAR-T cell therapy. Results: During an observation period up to 30 mo, B-NHL patients with higher baseline eosinophil counts had higher objective response rates than those with low eosinophil counts. Higher baseline eosinophil counts were also significantly associated with durable progression-free survival (PFS). The predictive significance of baseline eosinophil counts was validated in two independent cohorts. A preclinical model showed that eosinophil depletion impairs the intratumoral infiltration of transferred CAR-T cells and reduces CAR-T cell antitumor efficacy. Conclusion: The results of this study suggest that peripheral eosinophils could serve as stratification biomarkers and a recruitment machinery to facilitate anti-CD19 CAR-T cell therapy in B-NHL patients. © The author(s).

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出版当年[2021]版:
大类 | 1 区 医学
小类 | 1 区 医学:研究与实验
最新[2023]版:
大类 | 1 区 医学
小类 | 1 区 医学:研究与实验
第一作者:
第一作者机构: [1]Department of Oncology, Xinqiao Hospital, Army Medical University, Chongqing 400037, China. [2]Chongqing Key Laboratory of Immunotherapy, Chongqing 400037, China.
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通讯作者:
通讯机构: [1]Department of Oncology, Xinqiao Hospital, Army Medical University, Chongqing 400037, China. [2]Chongqing Key Laboratory of Immunotherapy, Chongqing 400037, China.
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