T-cell engagers in rheumatology

T-cell engagers (TCEs) have transformed the treatment of hematologic malignancies. Given the central role of B-cells in the pathogenesis of many autoimmune diseases, there has been growing interest in expanding the use of TCEs to rheumatologic indications as a simpler alternative to CAR-T.

This narrative review summarizes the biological rationale, structural diversity, dosing strategies, and emerging clinical efficacy and safety regarding the use of TCEs in rheumatology.

Among 12 studies reviewed, 80 patients received a TCE: 33 for SLE, 22 for RA, 14 for SSc, 6 for IIM, 2 for PSS, and 3 for other indications. Thirty-two patients received blinatumomab, 16 teclistamab, 15 mosunetuzumab, and 17 another TCE. Early signs of clinical improvement were observed, including rapid disease activity reduction, improvement in organ-specific manifestations, and normalization of serologic biomarkers. Nonetheless, many patients experienced persistent or recurrent disease activity after treatment discontinuation. There was substantial heterogeneity in dosing strategies across studies, with lower cumulative exposure and shorter treatment duration compared with regimens used in oncology, suggesting potential undertreatment may contribute to lower response rates and disease recurrence in some patients. CRS was observed in 46% of patients, of which 33% were grade 1, 12% were grade 2, and 1% was grade 3. No neurotoxicity or deaths have been reported.

TCEs demonstrated encouraging early efficacy and acceptable safety across several refractory autoimmune diseases, supporting their potential role as a novel therapeutic strategy. Longer prospective studies are needed to define adequate dosing schedules, long-term safety, and durability of response.