Cd3-Engaging Bispecific Antibodies Convert Human Regulatory T Cells into Cytotoxic Effectors (IMS 2026) - Sep 11, 2026 - Abstract #PA-068; Pres time: Sep 24, 2026; P2 | "11 patients were treated with teclistamab plus daratumumab, lenalidomide, and dexamethasone (Tec-DRD, n = 11) in the ongoing MajesTEC-5 (HD10/DSMMXX) trial (NCT05695508); 6 patients recived standard-of-care DRD as controls (n=6)...Generalizability was tested in vitro using three BTCEs (teclistamab (BCMA×CD3), blinatumomab (CD19×CD3), glofitamab (CD20×CD3)) to redirect primary human Tregs towards BCMA+, CD19+, and CD20+ cell lines... Our findings uncover a novel mechanism where BTCEs actively convert suppressive Tregs into cytotoxic, pro-inflammatory effectors that contribute to antitumor activity. Multi-color flow cytometry validates these dynamics in patients, showing a shift toward activated, cytotoxic memory Tregs. We identified the BATF/JUNB axis and IMiD-mediated Helios destabilization as targetable regulators of this process, supporting rational combination regimens to enhance T-cell-redirecting immunotherapies."
Bispecific • IO biomarker • Hematological Malignancies • Multiple Myeloma • FOXP3 • GZMA • IKZF2 • IL2RA • JUNB • NKG7 • TBX21
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Anna D. Metzler1; Julius J. Michel1; Jan H. Frenking1; Antonia Schach1; Erin W. Meermeier2; Vera Thiel1; Niklas Kehl3; Tim R. Wagner1; Julian Zoller3; Sven Cuntz1; Cornelius Funk1; René Onken1; Alanna Kirschner1; Stefanie Huhn4; Alexander Brobeil5; Andreas Trumpp1; Carsten Müller-Tidow6; Leif Bergsagel2; Hartmut Goldschmidt6; Hermann Einsele7; Leo Rasche7; Marta Chesi2; Marc S. Raab4; Niels Weinhold6; Mirco J. Friedrich1
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