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Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.

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Lymphoma-derived extracellular vesicles inhibit CAR T cell function.

Khadiza Siddika¹, Katie R Flaherty¹, Reuben Benjamin^2,3

¹Department of Infectious Diseases, King's College London, London, England, United Kingdom.

Micropublication Biology

|August 22, 2025

Summary

Lymphoma-derived extracellular vesicles (EV) can impair CD19-targeting CAR T cell therapy by transferring B cell markers and suppressing anti-tumour activity. This finding may explain treatment resistance in some B cell lymphoma patients.

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Area of Science:

Immunotherapy
Oncology
Cell Biology

Background:

CD19-targeting chimeric antigen receptor (CAR) T cell therapy is effective for relapsed/refractory B cell lymphoma.
Treatment resistance remains a challenge in CAR T cell therapy for lymphoma.

Purpose of the Study:

To investigate the impact of lymphoma-derived extracellular vesicles (EV) on CD19-targeting CAR T cell function.
To understand mechanisms of CAR T cell resistance in B cell lymphoma.

Main Methods:

In vitro co-culture experiments of CAR T cells with lymphoma-derived EVs.
Analysis of B cell marker expression (CD19, CD20) on CAR T cells.
Assessment of CAR T cell tumour-killing capacity.

Main Results:

Lymphoma-derived EVs express B cell markers CD19 and CD20.
These markers can transfer from EVs to the CAR T cell surface.
Lymphoma-EVs significantly suppress the tumour-killing function of CAR T cells in vitro.

Conclusions:

Lymphoma-derived EVs can negatively impact CD19-targeting CAR T cell efficacy.
EV-mediated marker transfer and functional suppression may contribute to CAR T cell resistance in B cell lymphoma.
Further research into targeting EV-mediated resistance is warranted.