Trial reportThe Journal of clinical investigation2016
CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients.
Trial report 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 6 registered trials, which are not on this map. Cited by 1,293 papers, 2 of them syntheses 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.
Phase I/II Study of Immunotherapy for Advanced CD19+ Chronic Lymphocytic Leukemia, Acute Lymphoblastic Leukemia/Lymphoma and Non-Hodgkin Lymphoma With Defined Subsets of Autologous T Cells Engineered to Express a CD19-Specific Chimeric Antigen Receptor
A Phase I Clinical Trial of T-Cells Targeting CD19 and CD22 for Subjects With CD19-positive Acute Lymphoblastic Leukemia
Safety and Efficacy of Anti-CD19 Chimeric Antigen Receptor-modified Autologous T Cells (CART19) in Patients with Relapsed/refractory CD19+ Acute Lymphoblastic Leukemia and Non-Hodgkin's Lymphoma. a Dose Escalation, Open-label, Phase I Study.
An Open-label Clinical Study on the Efficacy and Safety of CD7-specific CAR-T Cell Injection in the Treatment of CD7-positive Relapsed/Refractory Hematologic Tumors
A Phase 1 Multicenter, Open Label Trial Evaluating the Safety and Efficacy of DuoCAR20.19.22-D95 in Adult Patients With Relapsed or Refractory B-cell Malignancies
An Open-Label, Multicenter Phase 2-3 Clinical Study of Anti-CD19 Chimeric Antigen Receptor T Cells (Talikabtagene Autoleucel) in Patients With Relapsed/Refractory B-Cell Malignancies (NexCAR19)
Who cites it
1,293 citing papers in PubMed, 2 syntheses or guidelines pooled it, 2,064 citations in OpenAlex.
- American Society of Hematology 2026 guidelines for management of relapsed/refractory acute lymphoblastic leukemia in adolescents and young adults.Blood advances · 2026Guideline
- Biomarkers for predicting CAR-T cell therapy outcomes in B-cell acute lymphoblastic leukemia: a systematic review.Frontiers in immunology · 2025Pooled it
- Reprogramming engineered autologous T cells to overcome resistance in patients with Merkel cell carcinoma.Science translational medicine · 2026Trial
- Trial
- Tandem CD19/CD22 CAR T-cells as potential therapy for children and young adults with high-risk r/r B-ALL.EBioMedicine · 2025Trial
- 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
- Letetresgene Autoleucel in Advanced/Metastatic Myxoid/Round Cell Liposarcoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- Safety and Tolerability of Letetresgene Autoleucel (GSK3377794): Pilot Studies in Patients with Advanced Non-Small Cell Lung Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Case study of CD19 CAR T therapy in a subject with immune-mediate necrotizing myopathy treated in the RESET-Myositis phase I/II trial.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Trial
- Oncolytic virus OVV-03 enhances CAR-T cell therapy against glioblastoma via immune modulation and specific HER2 upregulation.Oncoimmunology · 2026Article
- From technological iteration to clinical breakthrough: advances of CAR-T cell therapy in autoimmune diseases.Annals of medicine · 2026Review
- Why CD4+ T cells matter in adoptive cell therapy for solid cancers.Immuno-oncology technology · 2026Review
- Research trends and hotspots of CAR-T cell therapy for acute lymphoblastic leukemia: A bibliometric analysis.Human vaccines & immunotherapeutics · 2026Article
- Model-Based Analysis with Mechanistic Insights to CAR-T-Cell Therapy Kinetics: Case Study with Axicabtagene Ciloleucel and Brexucabtagene Autoleucel.Clinical pharmacology and therapeutics · 2026Article
- Multi-dimensional orchestration of binders for improved CAR-T immunotherapy.Cancer letters · 2026Review
- Decentralized CAR-T production: clinical, economic, and regulatory perspectives. Worldwide Network for Blood & Marrow Transplantation (WBMT) special article.Bone marrow transplantation · 2026Review
- Generation of effector CD4Stem cell reports · 2026Article
- Immune tolerance platforms to mitigate unwanted immune responses.Journal of pharmaceutical sciences · 2026Review
- Article
- Humoral immunity in cancer.Signal transduction and targeted therapy · 2026Review
1,233 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
23 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundT cells that have been modified to express a CD19-specific chimeric antigen receptor (CAR) have antitumor activity in B cell malignancies; however, identification of the factors that determine toxicity and efficacy of these T cells has been challenging in prior studies in which phenotypically heterogeneous CAR-T cell products were prepared from unselected T cells.
methodsWe conducted a clinical trial to evaluate CD19 CAR-T cells that were manufactured from defined CD4+ and CD8+ T cell subsets and administered in a defined CD4+:CD8+ composition to adults with B cell acute lymphoblastic leukemia after lymphodepletion chemotherapy.
resultsThe defined composition product was remarkably potent, as 27 of 29 patients (93%) achieved BM remission, as determined by flow cytometry. We established that high CAR-T cell doses and tumor burden increase the risks of severe cytokine release syndrome and neurotoxicity. Moreover, we identified serum biomarkers that allow testing of early intervention strategies in patients at the highest risk of toxicity. Risk-stratified CAR-T cell dosing based on BM disease burden decreased toxicity. CD8+ T cell-mediated anti-CAR transgene product immune responses developed after CAR-T cell infusion in some patients, limited CAR-T cell persistence, and increased relapse risk. Addition of fludarabine to the lymphodepletion regimen improved CAR-T cell persistence and disease-free survival.
conclusionImmunotherapy with a CAR-T cell product of defined composition enabled identification of factors that correlated with CAR-T cell expansion, persistence, and toxicity and facilitated design of lymphodepletion and CAR-T cell dosing strategies that mitigated toxicity and improved disease-free survival.
trial registrationClinicalTrials.gov NCT01865617.
fundingR01-CA136551; Life Science Development Fund; Juno Therapeutics; Bezos Family Foundation.
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.