biostudies-literatureUnknown11(15)Nguyen KAChimeric antigen receptor (CAR) T cells effectively treat B cell malignancies. However, CAR-T cells cause inflammatory toxicities such as cytokine release syndrome (CRS), which is in contrast to T cell receptor (TCR)-engineered T cells against various antigens that historically have rarely been associated with CRS. To study whether and how differences in receptor types affect the propensity for eliciting inflammatory responses in a model system wherein TCR and CAR target equalized sources of clinically relevant antigen, we discovered a CD22-specific TCR and compared it to CD22 CAR. Both CD22 TCR-T and CD22 CAR-T cells eradicated leukemia in xenografts, but only CD22 CAR-T cells induced dose-dependent systemic inflammation. Compared to TCR-T cells, CAR-T cells disproportionately upregulatedScience advanceseadq4297https://www.ebi.ac.uk/biostudies/studies/S-EPMC11980841biostudies-literatureCD22 TCR-engineered T cells exert antileukemia cytotoxicity without causing inflammatory responses.PMC11980841Rae ZDavies JSDraper LMMeyer TJIshii KZhang LHinrichs CSTaylor NAchar SRLiu ZMcIntosh CPNorberg SMKelly MCNguyen KAAltan-Bonnet GWu XfalseCD22 TCR-engineered T cells exert antileukemia cytotoxicity without causing inflammatory responses.Chimeric antigen receptor (CAR) T cells effectively treat B cell malignancies. However, CAR-T cells cause inflammatory toxicities such as cytokine release syndrome (CRS), which is in contrast to T cell receptor (TCR)-engineered T cells against various antigens that historically have rarely been associated with CRS. To study whether and how differences in receptor types affect the propensity for eliciting inflammatory responses in a model system wherein TCR and CAR target equalized sources of clinically relevant antigen, we discovered a CD22-specific TCR and compared it to CD22 CAR. Both CD22 TCR-T and CD22 CAR-T cells eradicated leukemia in xenografts, but only CD22 CAR-T cells induced dose-dependent systemic inflammation. Compared to TCR-T cells, CAR-T cells disproportionately upregulated2025-01-01T00:00:00Z2025 Apr2026-06-02T10:08:30.382Z2026-05-26T03:06:28.645ZS-EPMC119808414020308810.1126/sciadv.adq4297