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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: |
Rhein, Simone  ORCID: https://orcid.org/0000-0002-9445-2352, Çakmak-Görür, Neşe ORCID: https://orcid.org/0000-0001-7857-2461, Grunert, Corinna ORCID: https://orcid.org/0000-0001-8376-8629, Al-Tabatabaee, Sarah Hayder Jalal, Serin, Nazli, Leisegang, Matthias ORCID: https://orcid.org/0000-0003-3692-7142, Timiliotis, Stefanos, Ohlmeier, Luisa Sophie ORCID: https://orcid.org/0000-0002-3381-3003, Freund, Cäcilia ORCID: https://orcid.org/0000-0002-9260-0032, Willimsky, Gerald ORCID: https://orcid.org/0000-0002-9693-948X, Konietschke, Frank, Kieback, Elisa ORCID: https://orcid.org/0000-0003-3831-2846, Tasian, Sarah K., Chapuy, Bjoern, Keller, Ulrich ORCID: https://orcid.org/0000-0002-8485-1958, Blankenstein, Thomas ORCID: https://orcid.org/0000-0002-3357-4321, Pezzutto, Antonio ORCID: https://orcid.org/0000-0002-3246-4470 and Busse, Antonia ORCID: https://orcid.org/0000-0002-3470-6947
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| 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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