ArticleNature medicine2017
Donor CD19 CAR T cells exert potent graft-versus-lymphoma activity with diminished graft-versus-host activity.
Article in Nature medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
149 citing papers in PubMed, 1 synthesis or guideline pooled it, 218 citations in OpenAlex.
- Anti-CD 19 and anti-CD 20 CAR-modified T cells for B-cell malignancies: a systematic review and meta-analysis.Immunotherapy · 2017Pooled it
- Donor-derived CARCIK-CD19 cells engineered with Sleeping Beauty transposon in acute lymphoblastic leukemia relapsed after allogeneic transplantation.Blood cancer journal · 2025Trial
- Trial
- Preemptive low-dose interleukin-2 or DLI for late-onset minimal residual disease in acute leukemia or myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation.Annals of hematology · 2021Trial
- Article
- Recipient-derived vs. donor-derived CAR-T-cell therapy in relapsed B-cell acute lymphoblastic leukemia patients after transplantation: A multi-center retrospective study.Chinese medical journal · 2026Observational
- Intrinsic tumor cell line immunogenicity may drive CAR-independent T cell responses and confound CAR T cell preclinical modeling.Journal for immunotherapy of cancer · 2026Article
- The TCR in CAR T cell therapy: use it or lose it?Cancer gene therapy · 2026Review
- The T Cell Receptor: Molecular Sensor, Therapeutic Mediator and Probabilistic Driver of Adaptive Immunity.Immunological reviews · 2026Review
- Characterization of host immune cell infiltrate in human CAR T cell-mediated xenogeneic graft versus host disease in NSG mice.Veterinary pathology · 2026Article
- Article
- Chronic Graft-versus-host Disease, Part 1: How Preclinical Models Shape Our Understanding of Biology and Pave the Way for Future Therapeutic Interventions.Transplantation · 2025Review
- Allogeneic NKG2D CAR-T Cell Therapy: A Promising Approach for Treating Solid Tumors.Biomedicines · 2025Review
- CAR T-cell immunotherapy as the next horizon in cancer eradication: current landscape, challenges, and future directions.Medical oncology (Northwood, London, England) · 2025Review
- Identification of Common Cancer Antigens Useful for Specific Immunotherapies to Colorectal Cancer and Liver Metastases.International journal of molecular sciences · 2025Article
- Engineering the next generation of allogeneic CAR cells: iPSCs as a scalable and editable platform.Stem cell reports · 2025Review
- Less frequent complications following CAR T-cell therapies: hemophagocytic lymphohistiocytosis, graft-versus-host disease, thrombotic microangiopathy, coagulation disorders and secondary malignancies: best practice recommendations from the EBMT Practice Harmonization and Guidelines Committee.Bone marrow transplantation · 2025Review
- CAR-mediated target recognition limits TCR-mediated target recognition of TCR- and CAR-dual-receptor-edited T cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Targeting BCL11B in CAR-engineered lymphoid progenitors drives NK-like cell development with prolonged anti-leukemic activity.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Article
89 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 3 institutions in 1 country.
Funding
Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematological malignancies. However, graft-versus-host disease (GVHD) and relapse after allo-HSCT remain major impediments to the success of allo-HSCT. Chimeric antigen receptors (CARs) direct tumor cell recognition of adoptively transferred T cells. CD19 is an attractive CAR target, which is expressed in most B cell malignancies, as well as in healthy B cells. Clinical trials using autologous CD19-targeted T cells have shown remarkable promise in various B cell malignancies. However, the use of allogeneic CAR T cells poses a concern in that it may increase risk of the occurrence of GVHD, although this has not been reported in selected patients infused with donor-derived CD19 CAR T cells after allo-HSCT. To understand the mechanism whereby allogeneic CD19 CAR T cells may mediate anti-lymphoma activity without causing a significant increase in the incidence of GVHD, we studied donor-derived CD19 CAR T cells in allo-HSCT and lymphoma models in mice. We demonstrate that alloreactive T cells expressing CD28-costimulated CD19 CARs experience enhanced stimulation, resulting in the progressive loss of both their effector function and proliferative potential, clonal deletion, and significantly decreased occurrence of GVHD. Concurrently, the other CAR T cells that were present in bulk donor T cell populations retained their anti-lymphoma activity in accordance with the requirement that both the T cell receptor (TCR) and CAR be engaged to accelerate T cell exhaustion. In contrast, first-generation and 4-1BB-costimulated CAR T cells increased the occurrence of GVHD. These findings could explain the reduced risk of GVHD occurring with cumulative TCR and CAR signaling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.