ArticleMolecular and cellular biology2018
CD19 Alterations Emerging after CD19-Directed Immunotherapy Cause Retention of the Misfolded Protein in the Endoplasmic Reticulum.
Article in Molecular and cellular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 57 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.
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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.
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Who cites it
57 citing papers in PubMed, 80 citations in OpenAlex.
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- Safety and clinical outcomes of a first-in-human trial of point-of-care manufactured trispecific CAR T cells targeting CD19, CD20, and CD22.Research square · 2026Article
- The race between 4-1BB- and CD28-based CD19 CAR-T products in the therapy of B-cell malignancies.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- Resistance mechanisms and overcoming strategies for CAR T-cell therapy in B-cell hematologic malignancies.Frontiers in immunology · 2026Review
- Research progress on resistance mechanisms to CAR-T cell therapy in diffuse large B-cell lymphoma.Frontiers in oncology · 2026Review
- CD19 exon 2 skipping is a potential prognostic correlate of anti-CD19 CAR-T therapy relapse.Frontiers in molecular medicine · 2026Article
- Truncated CD19 as a selection marker for the isolation of stem cell-derived β-cells.Disease models & mechanisms · 2026Article
- CD19-negative relapse after CAR-T cell therapy: mechanisms of antigen escape and lineage switch.Frontiers in immunology · 2026Review
- Innovative gene engineering strategies to address tumor antigen escape in cell therapy.Journal of translational medicine · 2025Review
- Facts and Hopes: CAR T-Cell Therapy and Immune Contexture in Non-Hodgkin Lymphoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- Mechanisms of Resistance to CAR T-Cells and How to Overcome Them.Methods and protocols · 2025Review
- NRCAM variant defined by microexon skipping is a targetable cell surface proteoform in high-grade gliomas.Cell reports · 2025Article
- The costimulatory domain influences CD19 CAR-T cell resistance development in B-cell malignancies.bioRxiv : the preprint server for biology · 2025Article
- Engineering immunity with CAR-NK cells: advancing the frontiers of cancer immunotherapy.Frontiers in pharmacology · 2025Review
- Precision immunotherapy with CAR-T cells in pediatric B-cell acute lymphoblastic leukemia: advances and unanswered challenges.Frontiers in oncology · 2025Review
- CAR T-cell-mediated delivery of bispecific innate immune cell engagers for neuroblastoma.Nature communications · 2024Article
- Bispecific antibodies and autologous chimeric antigen receptor T cell therapies for treatment of hematological malignancies.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Chimeric antigen receptor-induced antigen loss protects CD5.CART cells from fratricide without compromising on-target cytotoxicity.Cell reports. Medicine · 2024Article
- Overcoming the challenges of primary resistance and relapse after CAR-T cell therapy.Expert review of clinical immunology · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
We previously described a mechanism of acquired resistance of B-cell acute lymphoblastic leukemia to CD19-directed chimeric antigen receptor T-cell (CART) immunotherapy. It was based on in-frame insertions in or skipping of CD19 exon 2. To distinguish between epitope loss and defects in surface localization, we used retroviral transduction and genome editing to generate cell lines expressing CD19 exon 2 variants (CD19ex2vs) bearing vesicular stomatitis virus G protein (VSVg) tags. These lines were negative by live-cell flow cytometry with an anti-VSVg antibody and resistant to killing by VSVg-directed antibody-drug conjugates (ADCs), suggestive of a defect in surface localization. Indeed, pulse-chase and α-mannosidase inhibitor assays showed that all CD19ex2vs acquired endoplasmic reticulum (ER)-specific high-mannose-type sugars but not complex-type glycans synthesized in the Golgi apparatus. When fused with green fluorescent protein (GFP), CD19ex2vs (including a mutant lacking the relevant disulfide bond) showed colocalization with ER markers, implying protein misfolding. Mass spectrometric profiling of CD19-interacting proteins demonstrated that CD19ex2vs fail to bind to the key tetraspanin CD81 and instead interact with ER-resident chaperones, such as calnexin, and ER transporters involved in antigen presentation. Thus, even the intact domains of CD19ex2vs cannot be easily targeted with ADCs or current CD19 CARTs but could serve as sources of peptides for major histocompatibility complex (MHC)-restricted presentation and T-cell receptor (TCR)-mediated killing.
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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.