ArticleMolecular cancer2023
Safety and efficacy of a novel anti-CD19 chimeric antigen receptor T cell product targeting a membrane-proximal domain of CD19 with fast on- and off-rates against non-Hodgkin lymphoma: a first-in-human study.
Article in Molecular cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05338931 (An Open-label, Single-arm, Multi-center, Phase I/II Study to Evaluate the Safety, Tolerability, and Efficacy of AT101), which is not on this map. Cited by 19 papers.
What it found
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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, Single-arm, Multi-center, Phase I/II Study to Evaluate the Safety, Tolerability, and Efficacy of AT101 (Anti-CD19 Chimeric Antigen Receptor T Cell) in Patients With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma
Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Sequence and structural determinants of efficacious de novo chimaeric antigen receptors.Nature biomedical engineering · 2026Article
- Antibody format matters: A comparative analysis of VHH and scFv domains reveals superior in vivo CAR T cell function with VHH domains.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Cell-autonomous control of CAR signaling and receptor shedding via ADAM17-mediated proteolysis.Cell · 2026Article
- Mechanistic basis and therapeutic modulation of T cell fitness to enhance CAR-T cell efficacy in hematological malignancies.Frontiers in immunology · 2026Review
- Resistance mechanisms and overcoming strategies for CAR T-cell therapy in B-cell hematologic malignancies.Frontiers in immunology · 2026Review
- Sequence and structural determinants of efficaciousbioRxiv : the preprint server for biology · 2025Article
- Current status of chimeric antigen receptor T cell therapy and its exhaustion mechanism.Immunotherapy · 2025Review
- Mechanisms of Resistance to CAR T-Cells and How to Overcome Them.Methods and protocols · 2025Review
- Tandem CAR-T cells targeting mesothelin and MUC16 overcome tumor heterogeneity by targeting one antigen at a time.Journal for immunotherapy of cancer · 2025Article
- Increased functional potency of multi-edited CAR-T cells manufactured by a non-viral transfection system.Molecular therapy. Methods & clinical development · 2025Article
- Article
- Review
- Antitumor Activities of a Humanized Cancer-Specific Anti-HER2 Monoclonal Antibody, humHInternational journal of molecular sciences · 2025Article
- Real-world experience with tisagenlecleucel for the treatment of relapsed or refractory diffuse large B-cell lymphoma in Korea.Therapeutic advances in hematology · 2025Article
- Evolving strategies for addressing CAR T-cell toxicities.Cancer metastasis reviews · 2024Review
- Computational screening of the effects of mutations on protein-protein off-rates and dissociation mechanisms by τRAMD.Communications biology · 2024Article
- A Flow Cytometry-Based Method for Assessing CAR Cell Binding Kinetics Using Stable CAR Jurkat Cells.Bio-protocol · 2024Article
- The BTLA-HVEM axis restricts CAR T cell efficacy in cancer.Nature immunology · 2024Article
- MHC1/LILRB1 axis as an innate immune checkpoint for cancer therapy.Frontiers in immunology · 2024Review
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 10 institutions in 2 countries.
Funding
Abstract
backgroundCommercial anti-CD19 chimeric antigen receptor T-cell therapies (CART19) are efficacious against advanced B-cell non-Hodgkin lymphoma (NHL); however, most patients ultimately relapse. Several mechanisms contribute to this failure, including CD19-negative escape and CAR T dysfunction. All four commercial CART19 products utilize the FMC63 single-chain variable fragment (scFv) specific to a CD19 membrane-distal epitope and characterized by slow association (on) and dissociation (off) rates. We hypothesized that a novel anti-CD19 scFv that engages an alternative CD19 membrane-proximal epitope independent of FMC63 and that is characterized by faster on- and off-rates could mitigate CART19 failure and improve clinical efficacy.
methodsWe developed an autologous CART19 product with 4-1BB co-stimulation using a novel humanized chicken antibody (h1218). This antibody is specific to a membrane-proximal CD19 epitope and harbors faster on/off rates compared to FMC63. We tested h1218-CART19 in vitro and in vivo using FMC63-CART19-resistant models. We conducted a first-in-human multi-center phase I clinical trial to test AT101 (clinical-grade h1218-CART19) in patients with relapsed or refractory (r/r) NHL.
resultsPreclinically, h1218- but not FMC63-CART19 were able to effectively eradicate lymphomas expressing CD19 point mutations (L174V and R163L) or co-expressing FMC63-CAR19 as found in patients relapsing after FMC63-CART19. Furthermore, h1218-CART19 exhibited enhanced killing of B-cell malignancies in vitro and in vivo compared with FMC63-CART19. Mechanistically, we found that h1218-CART19 had reduced activation-induced cell death (AICD) and enhanced expansion compared to FMC63-CART19 owing to faster on- and off-rates. Based on these preclinical results, we performed a phase I dose-escalation trial, testing three dose levels (DL) of AT101 (the GMP version of h1218) using a 3 + 3 design. In 12 treated patients (7 DLBCL, 3 FL, 1 MCL, and 1 MZL), AT101 showed a promising safety profile with 8.3% grade 3 CRS (n = 1) and 8.3% grade 4 ICANS (n = 1). In the whole cohort, the overall response rate was 91.7%, with a complete response rate of 75.0%, which improved to 100% in DL-2 and -3. AT101 expansion correlates with CR and B-cell aplasia.
conclusionsWe developed a novel, safe, and potent CART19 product that recognizes a membrane-proximal domain of CD19 with fast on- and off-rates and showed significant efficacy and promising safety in patients with relapsed B-cell NHL.
trial registrationNCT05338931; Date: 2022-04-01.
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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.