期刊
LEUKEMIA
卷 31, 期 5, 页码 1087-1095出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/leu.2017.39
关键词
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资金
- European Commission Sixth Framework Program through the CHILDHOPE - Chimaeric T-cells for the treatment of paediatric cancers project (specific targeted research project STREP) [LSHC-CT-2006-037381]
- UK Leukaemia and Lymphoma Research Fund (Bloodwise)
- Children with Cancer UK
- UK Department of Health
- JP Moulton Charitable Foundation
- Deutsche Krebshilfe
- Deutsche Kinderkrebsstiftung
- Lowenkinder e.V
- Italian AIRC
- University College London Hospital
- Cancer Research UK [15953] Funding Source: researchfish
- Great Ormond Street Hospital Childrens Charity [W1105, W0911] Funding Source: researchfish
- National Institute for Health Research [NIHR-RP-R3-12-001] Funding Source: researchfish
- National Institutes of Health Research (NIHR) [NIHR-RP-R3-12-001] Funding Source: National Institutes of Health Research (NIHR)
Trials with second generation CD19 chimeric antigen receptors (CAR) T-cells report unprecedented responses but are associated with risk of cytokine release syndrome (CRS). Instead, we studied the use of donor Epstein-Barr virus-specific T-cells (EBV CTL) transduced with a first generation CD19CAR, relying on the endogenous T-cell receptor for proliferation. We conducted a multicenter phase I/II study of donor CD19CAR transduced EBV CTL in pediatric acute lymphoblastic leukaemia (ALL). Patients were eligible pre-emptively if they developed molecular relapse (>5x10(-4)) post first stem cell transplant (SCT), or prophylactically post second SCT. An initial cohort showed poor expansion/persistence. We therefore investigated EBV-directed vaccination to enhance expansion/persistence. Eleven patients were treated. No CRS, neurotoxicity or graft versus host disease (GVHD) was observed. At 1 month, 5 patients were in CR (4 continuing, 1 de novo), 1 PR, 3 had stable disease and 3 no response. At a median follow-up of 12 months, 10 of 11 have relapsed, 2 are alive with disease and 1 alive in CR 3 years. Although CD19CAR CTL expansion was poor, persistence was enhanced by vaccination. Median persistence was 0 (range: 0-28) days without vaccination compared to 56 (range: 0-221) days with vaccination (P=0.06). This study demonstrates the feasibility of multi-center studies of CAR T cell therapy and the potential for enhancing persistence with vaccination.
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