ArticleThe Journal of clinical investigation2016
Dual CD19 and CD123 targeting prevents antigen-loss relapses after CD19-directed immunotherapies.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03778346 (Integrin β7, BCMA, CS1, CD38 and CD138 as the Single or Compound Targets for the Fourth Genenation of CAR-T Cells), which is not on this map. Cited by 353 papers, 4 of them syntheses that pooled it.
What it found
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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.
Integrin β7, BCMA, CS1, CD38 and CD138 as the Single or Compound Targets for the Fourth Genenation of CAR-T Cells
Who cites it
353 citing papers in PubMed, 4 syntheses or guidelines pooled it, 551 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
- Strategies and mechanisms for the enhancement of chimeric antigen receptor T-cell functions.Science China. Life sciences · 2026Pooled it
- The role of chemokines and interleukins in acute lymphoblastic leukemia: a systematic review.Journal of applied biomedicine · 2024Pooled it
- Ligand-based CAR-T cell: Different strategies to drive T cells in future new treatments.Frontiers in immunology · 2022Pooled it
- Efficacy and safety of a novel CD19, CD22 dual-targeted fully human loop bi-CAR-T for the treatment of relapsed/refractory B cell non-Hodgkin lymphoma.Journal of translational medicine · 2025Trial
- Long-term activity of tandem CD19/CD20 CAR therapy in refractory/relapsed B-cell lymphoma: a single-arm, phase 1-2 trial.Leukemia · 2022Trial
- Co-expression of non-signaling CARs enhances EGFRvIII-specific CAR T-cell cytotoxicity against head and neck squamous cell carcinoma.BMC cancer · 2026Article
- IL-15 boosts mesothelin- and CD70-CAR NK cell potency in PDAC without added benefit from dual targeting.Molecular therapy. Oncology · 2026Article
- FOXP1 Knockdown Reprograms Th9 CAR-T Cells to Overcome Antigen Escape.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CAR T-cells in hematologic malignancies: Advances, challenges, and future directions.iScience · 2026Review
- Oncolytic adenoviruses encoding bispecific T cell engagers or a novel trispecific T cell engager for dual-targeting of c-MET and EGFR.Molecular therapy. Oncology · 2026Article
- Resistance mechanisms and overcoming strategies for CAR T-cell therapy in B-cell hematologic malignancies.Frontiers in immunology · 2026Review
- CD19-negative relapse after CAR-T cell therapy: mechanisms of antigen escape and lineage switch.Frontiers in immunology · 2026Review
- Bioengineered immunocompetent preclinical trial-on-chip tool enables screening of CAR T cell therapy for leukaemia.Nature biomedical engineering · 2025Article
- Protein catenation potentiates antitumor activity of malaria VAR2CSA navigation CAR-T cells in a mouse model of hematological malignancies.Journal for immunotherapy of cancer · 2025Article
- CAR-T cells in solid tumors: Challenges and breakthroughs.Cell reports. Medicine · 2025Review
- Optimal pairing of binder and co-stimulatory domains improves dual CART cell efficacy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Innovative gene engineering strategies to address tumor antigen escape in cell therapy.Journal of translational medicine · 2025Review
- Limitations of CAR-T-Cell Therapy in Hematologic Malignancies: Focusing on Antigen Escape and T-Cell Dysfunction.International journal of molecular sciences · 2025Review
- Computational structural optimization enhances IL13Rα2 - B7-H3 tandem CAR T cells to overcome antigen-heterogeneity-mediated tumor escape.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
293 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
21 authors at 4 institutions in 1 country.
Funding
Abstract
Potent CD19-directed immunotherapies, such as chimeric antigen receptor T cells (CART) and blinatumomab, have drastically changed the outcome of patients with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL). However, CD19-negative relapses have emerged as a major problem that is observed in approximately 30% of treated patients. Developing approaches to preventing and treating antigen-loss escapes would therefore represent a vertical advance in the field. Here, we found that in primary patient samples, the IL-3 receptor α chain CD123 was highly expressed on leukemia-initiating cells and CD19-negative blasts in bulk B-ALL at baseline and at relapse after CART19 administration. Using intravital imaging in an antigen-loss CD19-negative relapse xenograft model, we determined that CART123, but not CART19, recognized leukemic blasts, established protracted synapses, and eradicated CD19-negative leukemia, leading to prolonged survival. Furthermore, combining CART19 and CART123 prevented antigen-loss relapses in xenograft models. Finally, we devised a dual CAR-expressing construct that combined CD19- and CD123-mediated T cell activation and demonstrated that it provides superior in vivo activity against B-ALL compared with single-expressing CART or pooled combination CART. In conclusion, these findings indicate that targeting CD19 and CD123 on leukemic blasts represents an effective strategy for treating and preventing antigen-loss relapses occurring after CD19-directed therapies.
Indexed as
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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.