Trial reportJournal of translational medicine2025
Efficacy and safety of third-generation CD19-CAR T cells incorporating CD28 and TLR2 intracellular domains for B-cell malignancies with central nervous system involvement: results of a pivotal trial.
Trial report in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04605666 (CD19-Chimeric Antigen Receptor-T2 Cells for CD19 Positive Relapsed/Refractory B Cell Leukemia/Lymphoma), which is not on this map. Cited by 11 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.
CD19-Chimeric Antigen Receptor-T2 Cells for CD19 Positive Relapsed/Refractory B Cell Leukemia/Lymphoma
Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Safety and efficacy of CAR T-cell therapy in central nervous system lymphoma: a systematic review and meta-analysis.Frontiers in oncology · 2026Pooled it
- Breaching the Blood-Brain Barrier: Evolving Strategies for Central Nervous System Disease in Adult Acute Lymphoblastic Leukemia.Current hematologic malignancy reports · 2026Review
- CAR T-Cell Therapy in Neurology: A Scoping Review of Neuro-Oncology, Autoimmune Diseases & Neurotoxicity.Annals of clinical and translational neurology · 2026Article
- Challenges and advances in CAR-T cell therapy for B-ALL.Biomarker research · 2026Review
- CLL-1: An emerging target for immunotherapy in acute myeloid leukemia.Annals of hematology · 2026Review
- The trinity of T cell engagement: navigating the molecular and clinical landscape of CAR-T, TILs, and TCEs in the war against cancer.Frontiers in immunology · 2026Review
- CAR-T cell signaling dynamics, rational design principles and artificial intelligence for next-generation chimeric antigen receptors.Frontiers in immunology · 2026Review
- Advances in CAR-T therapy for central nervous system lymphoma.Frontiers in immunology · 2026Review
- Leukemia epidemiology in China: Burden, trends, and determinants in the 21st century.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2025Article
- Immune effector cell-associated neurotoxicity syndrome following CAR T-cell therapy: a review of recent advances.Journal of translational medicine · 2025Review
- Overview of Cellular Therapeutics Clinical Trials: Advances, Challenges, and Future Directions.International journal of molecular sciences · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors.
Funding
Abstract
backgroundThird‑generation CAR-T cells demonstrated promising efficacy and remarkably low toxicity in refractory or relapsed (R/R) B-cell malignancies. However, data on the patients with central nervous system (CNS) involvement are limited due to concerns regarding treatment-related neurotoxicity. This study aimed to evaluate the safety and efficacy of a novel third-generation anti-CD19 CAR T cells in patients with CNS involvement of B-cell malignancies.
methodsA total of 21 patients with R/R B-cell malignancies with CNS involvement, including 11 with B-cell acute lymphoblastic leukemia (B-ALL) and 10 with B-cell non-Hodgkin lymphoma (B-NHL) were enrolled. Patients derived lymphocytes were collected through apheresis and lentivirally transduced with the third-generation CAR incorporating both CD28 co-stimulation and TLR2-derived stimulatory domains (1928zT2). Patients received a single-dose 1928zT2 CAR-T cell infusion following lymphodepleting regimen. Safety, efficacy and cellular pharmacokinetics were investigated.
resultsOf the 21 patients with CNS involvement, the overall response rate (ORR) was 71% (15/21), with 73% (8/11) in B-ALL and 70% (7/10) in B-NHL. At a median follow-up of 20.4 months, median duration of response (DOR) was 11.1 months (95% CI, 2.9-24.4). 12-months progression-free survival (PFS) and overall survival (OS) estimates were 41.5% and 61.2%, respectively. Cytokine release syndrome (CRS) of any grade occurred in 20 patients (95%; grade ≥ 3 in 3 patients). Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 9 patients (42.8%; grade ≥ 3 in 6 patients). All CRS and ICANS events were manageable. The outcomes and adverse events are comparable between B-ALL and B-NHL patients. Notably, 1928zT2 CAR-T cells demonstrated blood-brain barrier penetrance, with subsequent detection in patient cerebrospinal fluid (CSF) correlating significantly with improved clinical outcomes.
conclusionsThird-generation 1928zT2 CAR-T cells are associated with high response rates, manageable safety and durable remissions in R/R B-cell malignancies with CNS involvement.
trial registrationClinicalTrials.gov, NCT04605666. Registered 1 May 2020.
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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 Socratic graph.