Trial reportThe Journal of clinical investigation2024
Drug-regulated CD33-targeted CAR T cells control AML using clinically optimized rapamycin dosing.
Trial report in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05105152 (Pediatric And Young Adult Leukemia Adoptive Therapy), which is not on this map. Cited by 41 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.
Pediatric And Young Adult Leukemia Adoptive Therapy (PLAT)-08: A Phase 1 Study Of SC-DARIC33 In Pediatric And Young Adults With Relapsed Or Refractory CD33+ AML
Who cites it
41 citing papers in PubMed, 2 syntheses or guidelines pooled it, 44 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
- Neuropsychiatric manifestations following chimeric antigen receptor T cell therapy for cancer: a systematic review of clinical outcomes and management strategies.Journal for immunotherapy of cancer · 2024Pooled it
- Preclinical advances and mechanistic insights of CAR-T therapy for acute myeloid leukemia: from target iteration to microenvironment regulation.Annals of medicine · 2026Review
- Enhanced CD33 CAR-NK cells secreting anti-CD73scFv overcome adenosine-mediated immunosuppression and improve anti-AML efficacy.Journal for immunotherapy of cancer · 2026Article
- Flavonoids of Rosa sterilis S. D. Shi alleviate high-fat diet-induced hyperlipidemia in mice by activation of autophagy.NPJ science of food · 2026Article
- Sialic acids modulate immune responses in cancer: Therapeutic opportunities.The Journal of biological chemistry · 2026Review
- Metabolic dysregulation reshapes the immune landscape: The gut microbiota-mTOR axis in respiratory viral infection immunity.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- The quintessential role for CAR T cell therapy in children, adolescents and young adults with cancer.Nature reviews. Clinical oncology · 2026Review
- Beyond CRISPR: next-gen precision engineering of CAR-NK cells for enhanced persistence, trafficking, and tumor eradication.Cancer cell international · 2026Review
- Sweet Surprises: Decoding Tumor-Associated Glycosylation in Cancer Progression and Therapeutic Potential.Cells · 2026Review
- Next-generation CAR-T therapy for acute myeloid leukemia: bridging innovation with clinical translation.Annals of hematology · 2026Review
- Engineering controllable CAR T-cell therapies: from binary safety switches to programmable immunity.Frontiers in immunology · 2026Review
- Immunological barriers and engineering strategies for CAR-T cell therapy in acute myeloid leukemia.Frontiers in immunology · 2026Review
- The transformative potential of lipid nanoparticles tailored for acute myeloid leukemia immunotherapy.Frontiers in immunology · 2026Review
- Humanized anti-CD33 CAR-T cells and antibody-drug conjugates for targeted therapy in acute myeloid leukemia.Frontiers in medicine · 2026Article
- Marine-Derived Quinolinone CHNQD-00603 Triggers Autophagy via Suppressing the AKT/ERK/mTOR Pathway to Reverse Senescence and Restore Osteogenic Potential in Bone Marrow Mesenchymal Stem Cells.Current protein & peptide science · 2026Article
- Review
- Have CARs stalled for non-B-cell malignancies? Where are we, and where are we going?Hematology. American Society of Hematology. Education Program · 2025Review
- Article
- Emerging strategies and novel therapeutic targets in acute myeloid leukemia: current advances and future directions.Biomarker research · 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
38 authors at 5 institutions in 1 country.
Funding
Abstract
Chimeric antigen receptor (CAR) designs that incorporate pharmacologic control are desirable; however, designs suitable for clinical translation are needed. We designed a fully human, rapamycin-regulated drug product for targeting CD33+ tumors called dimerizaing agent-regulated immunoreceptor complex (DARIC33). T cell products demonstrated target-specific and rapamycin-dependent cytokine release, transcriptional responses, cytotoxicity, and in vivo antileukemic activity in the presence of as little as 1 nM rapamycin. Rapamycin withdrawal paused DARIC33-stimulated T cell effector functions, which were restored following reexposure to rapamycin, demonstrating reversible effector function control. While rapamycin-regulated DARIC33 T cells were highly sensitive to target antigen, CD34+ stem cell colony-forming capacity was not impacted. We benchmarked DARIC33 potency relative to CD19 CAR T cells to estimate a T cell dose for clinical testing. In addition, we integrated in vitro and preclinical in vivo drug concentration thresholds for off-on state transitions, as well as murine and human rapamycin pharmacokinetics, to estimate a clinically applicable rapamycin dosing schedule. A phase I DARIC33 trial has been initiated (PLAT-08, NCT05105152), with initial evidence of rapamycin-regulated T cell activation and antitumor impact. Our findings provide evidence that the DARIC platform exhibits sensitive regulation and potency needed for clinical application to other important immunotherapy targets.
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.