ArticleJournal for immunotherapy of cancer2021
Single-cell multiomics dissection of basal and antigen-specific activation states of CD19-targeted CAR T cells.
Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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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
39 citing papers in PubMed, 53 citations in OpenAlex.
- A distinct CAR-T cell phenotype mediates therapeutic response at limited doses.Nature communications · 2026Trial
- Drug-regulated CD33-targeted CAR T cells control AML using clinically optimized rapamycin dosing.The Journal of clinical investigation · 2024Trial
- Artificial intelligence in oncology: linking biological discovery to clinical utility.Molecular cancer · 2026Review
- Mapping clinical CAR-T cells: insights from scRNA-seq.Trends in molecular medicine · 2026Review
- CAR T-cells in hematologic malignancies: Advances, challenges, and future directions.iScience · 2026Review
- Microfluidics for cell therapy and manufacturing in oncology and regenerative medicine.Lab on a chip · 2026Review
- Predictive markers for the efficacy of CAR T-cell therapy: the interplay between CAR T-cell fitness and systemic immunity.Blood advances · 2025Review
- Cytokine Engineering in CAR-T Cell Therapy: Next-Generation Strategies.Immune network · 2025Review
- Bioengineered immunocompetent preclinical trial-on-chip tool enables screening of CAR T cell therapy for leukaemia.Nature biomedical engineering · 2025Article
- Outcome correlates of approved CD19-targeted CAR T cells for large B cell lymphoma.Nature reviews. Clinical oncology · 2025Review
- Donor-derived GD2-specific CAR T cells in relapsed or refractory neuroblastoma.Nature medicine · 2025Article
- New insights on potency assays from recent advances and discoveries in CAR T-cell therapy.Frontiers in immunology · 2025Review
- Integrative single-cell multi-omics of CD19-CARCell reports. Medicine · 2024Article
- Article
- Toll-like receptor 4 signaling activation domains promote CAR T cell function against solid tumors.Molecular therapy. Oncology · 2024Article
- Challenges and opportunities in cancer immunotherapy: a Society for Immunotherapy of Cancer (SITC) strategic vision.Journal for immunotherapy of cancer · 2024Review
- Single-cell analysis of the survival mechanisms of fratricidal CAR-T targeting of T cell malignancies.Molecular therapy. Nucleic acids · 2024Article
- Harnessing the Transcriptional Signatures of CAR-T-Cells and Leukemia/Lymphoma Using Single-Cell Sequencing Technologies.International journal of molecular sciences · 2024Review
- Current progress in CAR-based therapy for kidney disease.Frontiers in immunology · 2024Review
- Unlocking ovarian cancer heterogeneity: advancing immunotherapy through single-cell transcriptomics.Frontiers in oncology · 2024Review
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundAutologous T cells engineered to express a chimeric antigen receptor (CAR) specific for CD19 molecule have transformed the therapeutic landscape in patients with highly refractory leukemia and lymphoma, and the use of donor-generated allogeneic CAR T is paving the way for further breakthroughs in the treatment of cancer. However, it remains unknown how the intrinsic heterogeneities of these engineered cells mediate therapeutic efficacy and whether allogeneic products match the effectiveness of autologous therapies.
methodsUsing single-cell mRNA sequencing in conjunction with CITE-seq, we performed multiomics characterization of CAR T cells generated from healthy donor and patients with acute lymphoblastic leukemia. CAR T cells used in this study were manufactured at the University of Pennsylvania through lentiviral transduction with a CD19-4-1BB-CD3ζ construct. Besides the baseline condition, we engineered NIH-3T3 cells with human CD19 or mesothelin expression to conduct ex vivo antigen-specific or non-antigen stimulation of CAR T cells through 6-hour coculture at a 1:1 ratio.
resultsWe delineated the global cellular and molecular CAR T landscape and identified that transcriptional CAR tonic signaling was regulated by a mixture of early activation, exhaustion signatures, and cytotoxic activities. On CD19 stimulation, we illuminated the disparities of CAR T cells derived from different origins and found that donor CAR T had more pronounced activation level in correlation with the upregulation of major histocompatibility complex class II genes compared with patient CAR T cells. This finding was independently validated in additional datasets from literature. Furthermore, GM-CSF(
conclusionsThrough integrated multiomics profiling and unbiased canonical pathway analyses, our results unveil heterogeneities in the transcriptional, phenotypic, functional, and metabolic profiles of donor and patient CAR T cells, providing mechanistic basis for ameliorating clinical outcomes and developing next-generation 'off- the-shelf' allogeneic products.
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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.