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| Item Type: | Article |
|---|---|
| Title: | A CD22-specific T-cell receptor enables effective adoptive T-cell therapy for B-cell malignancies |
| Creators Name: | Rhein, Simone, Çakmak-Görür, Neşe, Grunert, Corinna, Al-Tabatabaee, Sarah Hayder Jalal, Serin, Nazli, Leisegang, Matthias, Timiliotis, Stefanos, Ohlmeier, Luisa Sophie, Freund, Cäcilia, Willimsky, Gerald, Konietschke, Frank, Kieback, Elisa, Tasian, Sarah K., Chapuy, Bjoern, Keller, Ulrich, Blankenstein, Thomas, Pezzutto, Antonio and Busse, Antonia |
| Abstract: | CD19 chimeric antigen receptor (CAR) T-cell therapy has become the standard of care in relapse and/or refractory B-cell malignancies. Up to 30% to 60% of patients experience relapsed disease because of the emergence of CD19(low) or CD19(−) tumor cell clones. Although bispecific CD19/CD22 CAR T cells have been explored, limited persistence and antigen downregulation of CD19 and/or CD22 have compromised their efficacy in relapsing patients. A comprehensive analysis of CD22 expression revealed that CD22 is ubiquitously expressed across all subgroups of B-cell lymphomas and B-cell leukemias, establishing CD22 as a valuable immunotherapeutic target. Using a humanized mouse model with a diverse human T-cell receptor (TCR) repertoire, we identified a high-affinity TCR targeting a CD22 epitope presented by HLA-A*02:01. In vitro, this TCR demonstrated high specificity and efficacy in both CD22(+) cell lines and primary patient-derived tumor samples. Importantly, CD22 TCR T cells outperformed CD22 CAR T cells in recognizing cells with low CD22 surface expression, including CD22(low) Nalm6 cells that emerged after in vivo CD19 T-cell treatment. Unlike CD22 CAR T cells, CD22 TCR T cells effectively recognized tumor cells that predominantly express intracellular CD22. Notably, in vivo validation in a Nalm6 B-cell leukemia model confirmed the superior activity of CD22 TCR T cells against CD22(low) cells compared to CD22 CAR T cells. In conclusion, our findings provide strong preclinical evidence supporting CD22 TCR-based therapy as a potent treatment option for CD22(low) B-cell malignancies, including patients who relapsed after CD19 CAR T-cell therapy. |
| Keywords: | Adoptive Immunotherapy, B-Cell Leukemia, B-Cell Lymphoma, CD19 Antigens, Chimeric Antigen Receptors, Sialic Acid Binding Ig-Like Lectin 2, T-Cell Antigen Receptors, T-Lymphocytes, Tumor Cell Line, Animals, Mice |
| Source: | Blood |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Volume: | 147 |
| Number: | 10 |
| Page Range: | 1058-1069 |
| Date: | 5 March 2026 |
| Official Publication: | https://doi.org/10.1182/blood.2025029329 |
| PubMed: | View item in PubMed |
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