ArticleBlood2025
CD371-targeted CAR T cells secreting interleukin-18 exhibit robust expansion and clear refractory acute myeloid leukemia.
Article in Blood, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06017258 (Phase I Trial of CLEc12a), which is not on this map. Cited by 35 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 Trial of CLEc12a (CD371) Targeted ArmoRed Immune Effector Cells in Patients With Relapsed/Refractory Acute Myeloid Leukemia (CLEAR-AML)
Who cites it
35 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of acute leukemia, version 2.0.Journal for immunotherapy of cancer · 2026Guideline
- 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
- Minor histocompatibility antigen TCR-T.Blood advances · 2026Review
- Pediatric AML CAR T cell therapy.Molecular therapy. Oncology · 2026Review
- SRSF2 P95H induces monocytic priming of human hematopoietic stem and progenitor cells.Leukemia · 2026Article
- Chimeric antigen receptor (CAR)-T cell therapy for solid tumors in pediatric patients: current breakthroughs, dilemmas, and strategies.Experimental hematology & oncology · 2026Review
- A phase 1 trial of CD123-directed chimeric antigen receptor T-cell therapy in adults with relapsed/refractory acute myeloid leukemia or blastic plasmacytoid dendritic cell neoplasm.Journal of hematology & oncology · 2026Article
- Interleukin-18 armours antitumour immune effectors.Nature reviews. Immunology · 2026Review
- Phase 1 Study of KITE-222, an Autologous CLL-1-Directed CAR T-cell Therapy in Patients with Relapsed/Refractory Acute Myeloid Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Immunotherapy in acute myeloid leukemia: The antibodies, TriKEs, and CARs on the arduous road to cure.Blood reviews · 2026Review
- T cell-engaging bispecific antibodies for myeloid malignancies: Targets, formats, and clinical challenges.Cell reports. Medicine · 2026Review
- Engineering CAR-Vδ2 T cells to boost persistence and anti-tumor function.bioRxiv : the preprint server for biology · 2026Article
- The quintessential role for CAR T cell therapy in children, adolescents and young adults with cancer.Nature reviews. Clinical oncology · 2026Review
- IL-18 metabolically reprograms CAR-expressing natural killer T cells and enhances their antitumor activity.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Biomarker-empowered precision navigation of CAR-T cell therapy.Molecular cancer · 2026Review
- Beyond CAR-T and oncology: broadening chimeric antigen receptor technologies across cell types and diseases.Precision clinical medicine · 2026Review
- Cytokine-Engineered Chimeric Antigen Receptor-T Cell Therapy: How to Balance the Efficacy and Toxicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- FLT3-directed BiTE molecules vs CAR T cells in AML: costimulatory signals mitigate T-cell exhaustion.Blood advances · 2026Article
- Decoding the archipelago: single-cell biomarkers rechart the molecular geography of acute myeloid leukemia.Cell communication and signaling : CCS · 2026Review
Corrections and comments
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Authors and funding
31 authors.
Funding
Abstract
abstractSuccess of chimeric antigen receptor (CAR) T-cell therapy in lymphoid malignancies has not yet been recapitulated in acute myeloid leukemia (AML). We developed CAR T cells targeting CD371 with a mutated CD28 costimulatory domain to limit T-cell exhaustion, and constitutive interleukin-18 (IL-18) secretion to enhance immune function (CD371/SAVVY/IL-18 CAR). We initiated a phase 1 trial (NCT06017258), successfully manufactured and administered CD371/SAVVY/IL-18 CAR T cells in 5 patients with relapsed/refractory AML and observed expansion following a single infusion of 3 × 104 or 3 × 105 CAR T cells per kg; 3 patients refractory to ≥5 lines of therapy and postallogeneic transplant exhibited AML clearance and no evidence of graft-versus-host disease. Dose-limiting toxicity in the 2 patients treated with 3 × 105 CAR T cells per kg dose (prolonged cytopenias with marrow hypoplasia; severe cytokine release syndrome) led to dose reduction to 3 × 104 CAR T cells per kg in the following 3 patients. Single-cell analyses revealed that circulating CAR T cells in responders included predominantly cytotoxic CD8+ effector T cells 2 weeks after infusion while coexisting natural killer (NK) cells expressed markers of activation. This pilot study highlights the activity of low-dose IL-18 "armored" CAR T cells against refractory AML and their potential to promote CAR T-cell cytotoxicity and innate endogenous antitumor immunity. This trial was registered at www.ClinicalTrials.gov as #NCT06017258.
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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.