CD22 TCR-engineered T cells exert antileukemia cytotoxicity without causing inflammatory responses.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40203088.
- Also identified by DOI 10.1126/sciadv.adq4297 and PMC identifier 11980841.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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 upregulated inflammatory pathways without concordant augmentation in pathways involved in direct cytotoxicity upon antigen engagement. These differences in antileukemia responses comparing TCR-T and CAR-T cells highlight the potential opportunity to improve therapeutic safety by using TCRs.
Medical subject headings
- Sialic Acid Binding Ig-like Lectin 2
- Receptors, Chimeric Antigen
- Inflammation
- Receptors, Antigen, T-Cell
- T-Lymphocytes
- Immunotherapy, Adoptive
- Leukemia
- Cytotoxicity, Immunologic