ArticleCancer immunology, immunotherapy : CII2023
Host B cells escape CAR-T immunotherapy by reversible downregulation of CD19.
Article in Cancer immunology, immunotherapy : CII, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- The cellular landscape of druggable RNA-binding proteins.Nature reviews. Drug discovery · 2026Review
- A yeast surface display platform for characterizing CAR T cell responses to cancer antigens.Nature communications · 2025Article
- Mechanisms of Resistance to CAR T-Cells and How to Overcome Them.Methods and protocols · 2025Review
- Clinical Impact of CTLA-4 Single-Nucleotide Polymorphism in DLBCL Patients Treated with CAR-T Cell Therapy.Current oncology (Toronto, Ont.) · 2025Article
- The Potential Use of Digital Twin Technology for Advancing CAR-T Cell Therapy.Current issues in molecular biology · 2025Review
- Strategies to overcome tumour relapse caused by antigen escape after CAR T therapy.Molecular cancer · 2025Review
- Mechanisms of antigen-dependent resistance to chimeric antigen receptor (CAR)-T cell therapies.Cancer cell international · 2025Review
- Adoptive cell therapy against tumor immune evasion: mechanisms, innovations, and future directions.Frontiers in oncology · 2025Review
- SynNotch CAR-T cell, when synthetic biology and immunology meet again.Frontiers in immunology · 2025Review
- Finding Your CAR: The Road Ahead for Engineered T Cells.The American journal of pathology · 2024Review
- Failure of ALL recognition by CAR T cells: a review of CD 19-negative relapses after anti-CD 19 CAR-T treatment in B-ALL.Frontiers in immunology · 2023Review
- Treatment strategies for relapse after CAR T-cell therapy in B cell lymphoma.Frontiers in pediatrics · 2023Review
- Pushing the envelope: Immune mechanism and application landscape of macrophage-activating lipopeptide-2.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Anti-CD19-CAR-T cells are a successful clinical immunotherapy for B cell lymphomas, although some lymphomas can escape attack by downregulating surface CD19 levels. An undesirable consequence of this therapy is that it can also eliminate healthy B cells expressing CD19. Therefore, understanding the dynamics of CD19 expression in B cells under CAR-T cell immunotherapy can help mitigate both escape and adverse outcomes. Previous studies suggested that mechanisms responsible for the loss of CD19 expression in lymphomas usually involves genomic deletion or epigenetic modification which permanently removes CD19 as a therapeutic target in these cells. We examined if healthy B cells can use similar processes to lose CD19 expression and escape CAR-T attack. In the presence of CAR-T cells, untransformed B cells both when cultured in vitro or in vivo in non-tumor bearing animals downregulate expression of CD19. We then used adoptive transfer strategies to remove CD19-low B cells from αCD19-CAR-T pressure in vivo. Intriguingly, these B cells systematically recovered surface expression of CD19 comparable to wild-type levels. These data suggest that unlike many cases of lymphomas, healthy B cells downregulate CD19 in a reversible fashion. Taken together, these data suggest a dynamic regulatory process of CD19 surface expression on healthy B cells that could be exploited to modulate the expression of CD19 on cancer cells to improve immunotherapy or minimize the depletion of endogenous B cell compartment during treatment.
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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.