ArticleLeukemia2021
CAR T-cells that target acute B-lineage leukemia irrespective of CD19 expression.
Article in Leukemia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
102 citing papers in PubMed, 1 synthesis or guideline pooled it, 181 citations in OpenAlex.
- Mapping the clinical landscape of multifunctional CAR T cells: Targets, trends, and synergies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Pooled it
- Review
- In vivo CAR-T therapy: from molecular design to precision delivery.Journal of nanobiotechnology · 2026Review
- CD19-negative relapse after CAR-T cell therapy: mechanisms of antigen escape and lineage switch.Frontiers in immunology · 2026Review
- Research progress on resistance mechanisms to CAR-T cell therapy in diffuse large B-cell lymphoma.Frontiers in oncology · 2026Review
- Increased NFAT activity with dual CAR stimulation in CD19xCD22 CAR T-cells is associated with decreased exhaustion and improved survival.Journal for immunotherapy of cancer · 2025Article
- A Decade of Transformation in the Management of Childhood Acute Lymphoblastic Leukemia: From Conventional Chemotherapy to Precision Medicine.Pediatric reports · 2025Review
- Limitations of CAR-T-Cell Therapy in Hematologic Malignancies: Focusing on Antigen Escape and T-Cell Dysfunction.International journal of molecular sciences · 2025Review
- Endoglin-Directed CAR T Cells Comprehensively Target Tumors in Advanced Sarcomas.Cancer immunology research · 2025Article
- Mechanisms of Resistance to CAR T-Cells and How to Overcome Them.Methods and protocols · 2025Review
- Design of a water-soluble CD20 antigen with computational epitope scaffolding.Protein science : a publication of the Protein Society · 2025Article
- Current challenges and emerging opportunities of chimeric antigen receptor-engineered cell immunotherapy.Experimental hematology & oncology · 2025Review
- CAR Binders Affect CAR T-cell Tonic Signaling, Durability, and Sensitivity to Target.Cancer immunology research · 2025Article
- Article
- IKAROS levels are associated with antigen escape in CD19- and CD22-targeted therapies for B-cell malignancies.Nature communications · 2025Article
- Advances in Gene Therapy with Oncolytic Viruses and CAR-T Cells and Therapy-Related Groups.Current issues in molecular biology · 2025Review
- Review
- Molecular dynamics at immune synapse lipid rafts influence the cytolytic behavior of CAR T cells.Science advances · 2025Article
- Challenges in the preclinical design and assessment of CAR-T cells.Frontiers in immunology · 2025Review
- Bio-functional hydrogel coated membranes to decrease T-cell exhaustion in manufacturing of CAR T-cells.Frontiers in immunology · 2025Article
42 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
25 authors at 5 institutions in 2 countries.
Funding
Abstract
Chimeric antigen receptor (CAR) T-cells targeting CD19 demonstrate remarkable efficacy in treating B-lineage acute lymphoblastic leukemia (BL-ALL), yet up to 39% of treated patients relapse with CD19(-) disease. We report that CD19(-) escape is associated with downregulation, but preservation, of targetable expression of CD20 and CD22. Accordingly, we reasoned that broadening the spectrum of CD19CAR T-cells to include both CD20 and CD22 would enable them to target CD19(-) escape BL-ALL while preserving their upfront efficacy. We created a CD19/20/22-targeting CAR T-cell by coexpressing individual CAR molecules on a single T-cell using one tricistronic transgene. CD19/20/22CAR T-cells killed CD19(-) blasts from patients who relapsed after CD19CAR T-cell therapy and CRISPR/Cas9 CD19 knockout primary BL-ALL both in vitro and in an animal model, while CD19CAR T-cells were ineffective. At the subcellular level, CD19/20/22CAR T-cells formed dense immune synapses with target cells that mediated effective cytolytic complex formation, were efficient serial killers in single-cell tracking studies, and were as efficacious as CD19CAR T-cells against primary CD19(+) disease. In conclusion, independent of CD19 expression, CD19/20/22CAR T-cells could be used as salvage or front-line CAR therapy for patients with recalcitrant disease.
Indexed as
Identifiers
What OpenQuestion holds
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.