What question did this study set out to answer?

To investigate whether receptor architecture alters the risk of systemic inflammatory toxicity by comparing CD22-specific TCR-engineered T cells against CD22 CAR-T cells targeting the same antigen.

April 9, 2025Science AdvancesOpen Access

CD22 TCR-engineered T cells exert antileukemia cytotoxicity without causing inflammatory responses

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Authors

KNKilyna A. Nguyen ZLZhihui Liu JDJohn Davies

Discussion

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Overview

Preclinical study demonstrates CD22 TCR-T cells clear leukemia without systemic inflammation in xenografts, suggesting safer cell therapies.

Key Points

To investigate whether receptor architecture alters the risk of systemic inflammatory toxicity by comparing CD22-specific TCR-engineered T cells against CD22 CAR-T cells targeting the same antigen.
Identified and engineered a CD22-specific T cell receptor (TCR-T) to directly match the target antigen of CD22 chimeric antigen receptor (CAR-T) cells.
Evaluated antileukemia cytotoxicity and inflammatory responses of CD22 TCR-T versus CD22 CAR-T cells in leukemia xenograft models.
Assessed transcriptional pathways related to direct cytotoxicity and inflammatory signaling following antigen engagement.
Both CD22 TCR-T and CD22 CAR-T cells eradicated leukemia in xenograft models.
CD22 CAR-T cells induced dose-dependent systemic inflammation, whereas CD22 TCR-T cells did not trigger these toxic inflammatory responses.
CAR-T cells disproportionately upregulated inflammatory pathways compared to TCR-T cells, without showing a concordant increase in cytotoxic pathways upon antigen stimulation.

Cite This Study

Nguyen et al. (2025) studied this question.

synapsesocial.com/papers/6a18908bb1bf25371265fa1f https://doi.org/10.1126/sciadv.adq4297

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April 9, 2025Science AdvancesOpen Access

CD22 TCR-engineered T cells exert antileukemia cytotoxicity without causing inflammatory responses

View Full Paper

Ask AI

Bookmark

Authors

KNKilyna A. Nguyen ZLZhihui Liu JDJohn Davies

Discussion

Member takes

Overview

Preclinical study demonstrates CD22 TCR-T cells clear leukemia without systemic inflammation in xenografts, suggesting safer cell therapies.

Key Points

To investigate whether receptor architecture alters the risk of systemic inflammatory toxicity by comparing CD22-specific TCR-engineered T cells against CD22 CAR-T cells targeting the same antigen.
Identified and engineered a CD22-specific T cell receptor (TCR-T) to directly match the target antigen of CD22 chimeric antigen receptor (CAR-T) cells.
Evaluated antileukemia cytotoxicity and inflammatory responses of CD22 TCR-T versus CD22 CAR-T cells in leukemia xenograft models.
Assessed transcriptional pathways related to direct cytotoxicity and inflammatory signaling following antigen engagement.
Both CD22 TCR-T and CD22 CAR-T cells eradicated leukemia in xenograft models.
CD22 CAR-T cells induced dose-dependent systemic inflammation, whereas CD22 TCR-T cells did not trigger these toxic inflammatory responses.
CAR-T cells disproportionately upregulated inflammatory pathways compared to TCR-T cells, without showing a concordant increase in cytotoxic pathways upon antigen stimulation.

Cite This Study

Nguyen et al. (2025) studied this question.

synapsesocial.com/papers/6a18908bb1bf25371265fa1f https://doi.org/10.1126/sciadv.adq4297

Also Consider

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