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We are analyzing https://www.nature.com/articles/s43018-021-00207-7.

Title:
Clonal expansion of T memory stem cells determines early anti-leukemic responses and long-term CAR T cell persistence in patients | Nature Cancer
Description:
Low-affinity CD19 chimeric antigen receptor (CAR) T cells display enhanced expansion and persistence, enabling fate tracking through integration site analysis. Here we show that integration sites from early (1 month) and late (>3 yr) timepoints cluster separately, suggesting different clonal contribution to early responses and prolonged anti-leukemic surveillance. CAR T central and effector memory cells in patients with long-term persistence remained highly polyclonal, whereas diversity dropped rapidly in patients with limited CAR T persistence. Analysis of shared integrants between the CAR T cell product and post-infusion demonstrated that, despite their low frequency, T memory stem cell clones in the product contributed substantially to the circulating CAR T cell pools, during both early expansion and long-term persistence. Our data may help identify patients at risk of early loss of CAR T cells and highlight the critical role of T memory stem cells both in mediating early anti-leukemic responses and in long-term surveillance by CAR T cells. Amrolia and colleagues characterize the clonal origins of long-term persistent CAR T cells from the CARPALL trial using low-affinity CAR T cells mediating long-term anti-leukemic control in patients through TSCM-mediated responses.
Website Age:
30 years and 10 months (reg. 1994-08-11).

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  • Science
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Custom-built

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Keywords {🔍}

data, cells, cell, nature, relative, car, fig, panels, article, source, cancer, extended, early, patients, research, london, raw, datasets, figure, memory, access, stem, integration, product, gene, collected, plots, analysis, sites, study, number, content, persistence, med, google, scholar, therapy, information, expansion, longterm, biasco, chimeric, infusion, nat, top, shown, treatment, cookies, clonal, antigen,

Topics {✒️}

nature portfolio journals permissions reprints gene editing technology nature portfolio privacy policy ebv-specific t-cell infusions advertising shannon diversity index low-affinity cd19 car single-cell transcriptional profiling social media nihr research professorship prolonged anti-leukemic surveillance chimeric antigen receptor-modified nature https decade-long leukaemia remissions b-cell lymphoblastic leukemia acute lymphoblastic leukaemia steady-state reconstitution phases author information authors nature+ nature chimeric antigen receptor cd62l+cd45ra+cd95 expression university college london chimeric antigen receptors dana farber/boston children dana-farber/boston children extended data fig source data fig chronic lymphocytic leukemia supplementary information section permissions author correspondence springerlink instant access bilyana popova andre lopes long-term surveillance memory stem cells institutional subscriptions read long-term outcome gene therapy program cell immunological memory long-term persistence c1qb-expressing macrophages privacy treat leukemia remission author gene content long-term car

Schema {🗺️}

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      headline:Clonal expansion of T memory stem cells determines early anti-leukemic responses and long-term CAR T cell persistence in patients
      description:Low-affinity CD19 chimeric antigen receptor (CAR) T cells display enhanced expansion and persistence, enabling fate tracking through integration site analysis. Here we show that integration sites from early (1 month) and late (>3 yr) timepoints cluster separately, suggesting different clonal contribution to early responses and prolonged anti-leukemic surveillance. CAR T central and effector memory cells in patients with long-term persistence remained highly polyclonal, whereas diversity dropped rapidly in patients with limited CAR T persistence. Analysis of shared integrants between the CAR T cell product and post-infusion demonstrated that, despite their low frequency, T memory stem cell clones in the product contributed substantially to the circulating CAR T cell pools, during both early expansion and long-term persistence. Our data may help identify patients at risk of early loss of CAR T cells and highlight the critical role of T memory stem cells both in mediating early anti-leukemic responses and in long-term surveillance by CAR T cells. Amrolia and colleagues characterize the clonal origins of long-term persistent CAR T cells from the CARPALL trial using low-affinity CAR T cells mediating long-term anti-leukemic control in patients through TSCM-mediated responses.
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            address:
               name:Molecular and Cellular Immunology Section, UCL Great Ormond Street Institute of Child Health, London, UK
               type:PostalAddress
            type:Organization
      name:Aleks Guvenel
      affiliation:
            name:UCL Great Ormond Street Institute of Child Health
            address:
               name:Molecular and Cellular Immunology Section, UCL Great Ormond Street Institute of Child Health, London, UK
               type:PostalAddress
            type:Organization
      name:Rachael Hough
      affiliation:
            name:University College London Hospital
            address:
               name:Department of Haematology, University College London Hospital, London, UK
               type:PostalAddress
            type:Organization
      name:Robert Wynn
      affiliation:
            name:Royal Manchester Children’s Hospital
            address:
               name:Department of Bone Marrow Transplant, Royal Manchester Children’s Hospital, Manchester, UK
               type:PostalAddress
            type:Organization
      name:Bilyana Popova
      affiliation:
            name:University College London
            address:
               name:CRUK UCL Cancer Trials Centre, University College London, London, UK
               type:PostalAddress
            type:Organization
      name:Andre Lopes
      affiliation:
            name:University College London
            address:
               name:CRUK UCL Cancer Trials Centre, University College London, London, UK
               type:PostalAddress
            type:Organization
      name:Martin Pule
      affiliation:
            name:University College London Cancer Institute
            address:
               name:University College London Cancer Institute, London, UK
               type:PostalAddress
            type:Organization
      name:Adrian J. Thrasher
      affiliation:
            name:UCL Great Ormond Street Institute of Child Health
            address:
               name:Molecular and Cellular Immunology Section, UCL Great Ormond Street Institute of Child Health, London, UK
               type:PostalAddress
            type:Organization
      name:Persis J. Amrolia
      url:http://orcid.org/0000-0003-0480-3911
      affiliation:
            name:UCL Great Ormond Street Institute of Child Health
            address:
               name:Molecular and Cellular Immunology Section, UCL Great Ormond Street Institute of Child Health, London, UK
               type:PostalAddress
            type:Organization
            name:Great Ormond Street Hospital
            address:
               name:Department of Bone Marrow Transplantation, Great Ormond Street Hospital, London, UK
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Molecular and Cellular Immunology Section, UCL Great Ormond Street Institute of Child Health, London, UK
      name:Gene Therapy Program, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Harvard Medical School, Boston, USA
      name:Molecular and Cellular Immunology Section, UCL Great Ormond Street Institute of Child Health, London, UK
      name:Molecular and Cellular Immunology Section, UCL Great Ormond Street Institute of Child Health, London, UK
      name:Molecular Haematology Section, UCL Great Ormond Street Institute of Child Health, London, UK
      name:Molecular and Cellular Immunology Section, UCL Great Ormond Street Institute of Child Health, London, UK
      name:Molecular and Cellular Immunology Section, UCL Great Ormond Street Institute of Child Health, London, UK
      name:Department of Haematology, University College London Hospital, London, UK
      name:Department of Bone Marrow Transplant, Royal Manchester Children’s Hospital, Manchester, UK
      name:CRUK UCL Cancer Trials Centre, University College London, London, UK
      name:CRUK UCL Cancer Trials Centre, University College London, London, UK
      name:University College London Cancer Institute, London, UK
      name:Molecular and Cellular Immunology Section, UCL Great Ormond Street Institute of Child Health, London, UK
      name:Molecular and Cellular Immunology Section, UCL Great Ormond Street Institute of Child Health, London, UK
      name:Department of Bone Marrow Transplantation, Great Ormond Street Hospital, London, UK
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