Development of a CD22-specific TCR for B-cell malignancies
Rhein S, Çakmak-Görür N, Grunert C, et al. A CD22-Specific T-Cell Receptor Enables Effective Adoptive T-Cell Therapy for B-Cell Malignancies. Blood. 2025; (doi: 10.1182/blood.2025029329).
Owing to its consistent presence in B-cell lymphomas and leukemias, researchers tout CD22's promise as a therapeutic target, but they suspect chimeric antigen receptor (CAR) immunotherapy may not be the best pathway to harness that potential. Scientists employing a murine model populated by diverse human T-cell receptors (TCRs) identified one with high affinity for targeting an HLA-A*02:01-restricted CD22 epitope. In vitro, the same TCR exhibited robust specificity and efficacy in CD22-positive cell lines and in tumor samples extracted from patients. CD22 TCR T-cells were also better than CD22 CAR T-cells at recognizing cells with low CD22 surface expression and high intracellular expression. The preclinical evidence favors CD22 TCR-based therapy as an intervention in the setting of CD22low B-cell malignancies, which commonly present in patients who relapse after CD19- or CD22-directed CAR T-cell therapy.