ArticleBlood2016
Murine allogeneic CD19 CAR T cells harbor potent antileukemic activity but have the potential to mediate lethal GVHD.
Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 111 citations in OpenAlex.
- Boosting T cell antioxidant capacity: A strategic approach to overcome immunosuppression in solid tumors.Redox biology · 2026Review
- Chronic graft-versus-host disease.Nature reviews. Disease primers · 2026Review
- Current and emerging maintenance strategies after stem cell transplantation in children and adolescents with acute leukemias.Molecular therapy. Oncology · 2026Review
- Pre-Treatment with Dacarbazine Sensitizes B16 Melanoma to CAR T Cell Therapy in Syngeneic Mouse Model.International journal of molecular sciences · 2025Article
- Challenging go/no-go decision scenarios and design recommendations in phase II oncology trials.Journal of the National Cancer Center · 2025Article
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- Immunotherapy for precision medicine in colorectal cancer.Expert review of precision medicine and drug development · 2025Article
- Universal CAR-T Cell Therapy for Cancer Treatment: Advances and Challenges.Oncology research · 2025Review
- Improved safety of chimeric antigen receptor T cells indirectly targeting antigens via switchable adapters.Nature communications · 2024Article
- Review
- Enhanced non-viral gene delivery via calcium phosphate/DNA co-precipitates with low-voltage pulse electroporation in NK-92 cells for immunocellular therapy.APL bioengineering · 2024Article
- Deleting the mitochondrial respiration negative regulator MCJ enhances the efficacy of CD8Nature communications · 2024Article
- Molecular understanding and clinical outcomes of CAR T cell therapy in the treatment of urological tumors.Cell death & disease · 2024Review
- Granzyme F: Exhaustion Marker and Modulator of Chimeric Antigen Receptor T Cell-Mediated Cytotoxicity.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- A CD3 humanized mouse model unmasked unique features of T-cell responses to bispecific antibody treatment.Blood advances · 2024Article
- [Safety and efficacy of donor-derived chimeric antigen receptor T-cell therapy in patients with relapsed B-cell acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2024Article
- Harnessing Chimeric Antigen Receptor-engineered Invariant Natural Killer T Cells: Therapeutic Strategies for Cancer and the Tumor Microenvironment.Current pharmaceutical biotechnology · 2024Review
- The 4-1BBζ costimulatory domain in chimeric antigen receptors enhances CD8+ T-cell functionality following T-cell receptor stimulation.Cancer cell international · 2023Article
- CAR-T Cell Therapy: From the Shop to Cancer Therapy.International journal of molecular sciences · 2023Review
12 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Acute lymphoblastic leukemia (ALL) persisting or relapsing following bone marrow transplantation (BMT) has a dismal prognosis. Success with chimeric antigen receptor (CAR) T cells offers an opportunity to treat these patients with leukemia-redirected donor-derived T cells, which may be more functional than T cells derived from patients with leukemia but have the potential to mediate graft-versus-host disease (GVHD). We, together with others, have previously demonstrated tumor-specific T-cell dysfunction in the allogeneic environment. Here, we studied CAR T-cell function following BMT using an immunocompetent murine model of minor mismatched allogeneic transplantation followed by donor-derived CD19-CAR T cells. Allogeneic donor-derived CD19-CAR T cells eliminated residual ALL with equal potency to those administered after syngeneic BMT. Surprisingly, allogeneic CAR T cells mediated lethal acute GVHD with early mortality, which is atypical for this minor mismatch model. We demonstrated that both allogeneic and syngeneic CAR T cells show initial expansion as effector T cells, with a higher peak but rapid deletion of allogeneic CAR T cells. Interestingly, CAR-mediated acute GVHD was only seen in the presence of leukemia, suggesting CAR-target interactions induced GVHD. Indeed, serum interleukin (IL)-6 was elevated only in the presence of both leukemia and CAR T cells, and IL-6 neutralization ameliorated the severity of GVHD in a delayed donor lymphocyte infusion model. Finally, allogeneic CD4(+) CAR T cells were responsible for GVHD, which correlated with their ability to produce IL-6 upon CAR stimulation. Altogether, we demonstrate that donor-derived allogeneic CAR T cells are active but have the capacity to drive GVHD.
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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.