Related Experiment Video
Updated: Feb 3, 2026

Studying Interactions between Myeloid Cells and CAR T Cells In Vitro and In Vivo
Published on: July 25, 2025
Abstract:
A case report highlights a novel, rare mechanism of resistance to chimeric antigen receptor (CAR) T-cell therapy, conferred by the accidental transduction of a single leukemic B cell with the anti-CD19 CAR (CAR19) gene during therapy manufacturing. Because CAR19 bound directly to CD19 on the cell surface-a phenomenon called in cis epitope masking-the therapeutic target was effectively hidden from reprogrammed T cells.
Insights
A rare resistance mechanism to chimeric antigen receptor (CAR) T-cell therapy was observed. Accidental gene transfer masked the cancer target, hiding it from CAR T-cells.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Chimeric antigen receptor (CAR) T-cell therapy is a promising cancer treatment.
- Resistance to CAR T-cell therapy can limit treatment efficacy.
Discussion:
- A case report identified a novel resistance mechanism to anti-CD19 CAR T-cell therapy.
- This resistance occurred due to accidental transduction of a leukemic B cell with the CAR19 gene during manufacturing.
- The CAR19 protein on the B cell surface masked the CD19 target, preventing CAR T-cell recognition.
Key Insights:
- In cis epitope masking is a rare mechanism of CAR T-cell resistance.
- This phenomenon highlights manufacturing-related risks in CAR T-cell therapy.
- Understanding resistance mechanisms is crucial for improving CAR T-cell therapy outcomes.
Outlook:
- Further research is needed to explore the frequency and implications of in cis epitope masking.
- Strategies to mitigate manufacturing-induced resistance should be investigated.
- This finding may inform the development of next-generation CAR T-cell therapies.
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