ReviewNature reviews. Clinical oncology2021
A comparison of chimeric antigen receptors containing CD28 versus 4-1BB costimulatory domains.
Review in Nature reviews. Clinical oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07502118 (An Open-Label, Multicenter Phase 2-3 Clinical Study of Anti-CD19 Chimeric Antigen Receptor T Cells), which is not on this map. Cited by 252 papers, 6 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.
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
252 citing papers in PubMed, 6 syntheses or guidelines pooled it, 369 citations in OpenAlex.
- Predictive value of preclinical models for CAR-T cell therapy clinical trials: a systematic review and meta-analysis.Journal for immunotherapy of cancer · 2025Pooled it
- Efficacy and safety of CD19 combined with CD22 or CD20 chimeric antigen receptor T-cell therapy for hematological malignancies.Frontiers in immunology · 2025Pooled it
- Comprehensive analysis of the efficacy and safety of CAR T-cell therapy in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia: a systematic review and meta-analysis.Annals of medicine · 2024Pooled it
- Pooled it
- Axicabtagene Ciloleucel versus Tisagenlecleucel for Relapsed or Refractory Large B Cell Lymphoma: A Systematic Review and Meta-Analysis.Transplantation and cellular therapy · 2024Pooled it
- Clinical efficacy and safety of combined anti-BCMA and anti-CD19 CAR-T cell therapy for relapsed/refractory multiple myeloma: a systematic review and meta-analysis.Frontiers in oncology · 2024Pooled it
- 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
- Tumor microenvironment biomarkers predicting pathological response to neoadjuvant chemoimmunotherapy in locally advanced esophageal squamous cell carcinoma: post-hoc analysis of a single center, phase 2 study.Journal for immunotherapy of cancer · 2024Trial
- Review
- Immune effector cell-associated hematotoxicity following CAR-T cell therapies: insights from a large national database.Japanese journal of clinical oncology · 2026Article
- CAR-T therapy for immune-mediated necrotizing myopathy: a review of mechanisms and emerging clinical evidence.Clinical rheumatology · 2026Review
- Development of chimeric antigen receptors targeting the γδ T cell receptor.Molecular therapy. Oncology · 2026Article
- Chimeric antigen receptor (CAR)-T cell therapy for solid tumors in pediatric patients: current breakthroughs, dilemmas, and strategies.Experimental hematology & oncology · 2026Review
- T cell senescence and exhaustion: molecular mechanisms and immune rejuvenation for cancer immunotherapy.Signal transduction and targeted therapy · 2026Review
- Investigating the role of costimulatory domains in enhancing CAR-T cell persistence in TNBC.Cancer gene therapy · 2026Review
- Cellular therapies in systemic lupus erythematosus: recent progress and future directions.Clinical rheumatology · 2026Review
- Advances and prospects in cell therapy for cancer: explorations from T cells to stem cells.Signal transduction and targeted therapy · 2026Review
- Efficacy and Safety of Lisocabtagene Maraleucel in Relapsed or Refractory Large B-Cell Lymphoma: A Product-Specific Systematic Review and Meta-Analysis of Clinical Trials and Real-World Studies.Hematology reports · 2026Review
- Novel approaches to modulate CAR-T cell function by targeting the tumor microenvironment in ovarian cancer.Journal of ovarian research · 2026Review
- The evolving landscape of CAR T cell therapy in children and young adults with B cell acute lymphoblastic leukemia.Molecular therapy. Oncology · 2026Review
192 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
2 authors at 2 institutions in 1 country.
Funding
Abstract
Chimeric antigen receptors (CARs) are engineered proteins designed to target T cells to cancer cells. To effectively activate the T cells in which they are expressed, CARs must contain a costimulatory domain. The CAR T cell products approved for the treatment of B cell lymphomas and/or acute lymphoblastic leukaemia or multiple myeloma incorporate either a CD28-derived or a 4-1BB-derived costimulatory domain. Almost all other clinically tested CARs also use costimulatory domains from CD28 or 4-1BB. In preclinical experiments, cytokine release is usually greater with CARs containing CD28 versus 4-1BB costimulatory domains; however, constructs with either domain confer similar anticancer activity in mouse models. T cell products expressing CARs with either CD28 or 4-1BB costimulatory domains have been highly efficacious in patients with relapsed haematological malignancies, with anti-CD19 products having similar activity regardless of the source of the costimulatory domain. In large-cohort clinical trials, the rates of neurological toxicities have been higher with CD28-costimulated CARs, although this finding is probably the result of a combination of factors rather than due to CD28 signalling alone. Future preclinical and clinical research should aim to compare different costimulatory domains while controlling for confounding variables. Herein, we provide an overview of T cell costimulation by CD28 and 4-1BB and, using the available preclinical and clinical data, compare the efficacy and toxicity profiles associated with CARs containing either costimulatory domain.
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.