From BiTE to TriTE: Progress of T-cell Engagers in RMDs Save

The EULAR 2026 Congress in London showcased growing interest in T-cell engagers as a novel strategy to achieve deep B-cell depletion and drug-free remission in refractory rheumatic and musculoskeletal diseases (RMDs). Bispecific T-cell engagers (BiTE) aim to overcome limitations of CAR-T therapies through immediate off-the-shelf availability, reversible toxicity due to short half-life of these monoclonal antibodies, avoid the need for conditioning/lymphodepletion, and lower cost. 

Below is a review of 3 notable abstracts highlighting the progress of  T-cell engager technologies in RMDs. 

In (OP0203), Bucci and colleagues presented data from an open-label study evaluating low-dose blinatumomab, a CD19×CD3 bispecific T-cell engager, in 15 patients with multidrug-resistant rheumatoid arthritis (RA) i.e. at least failure to 2 b/tsDMARDs. Treatment with blinatumomab resulted in deep peripheral and synovial depletion but not in the lymph nodes. However, treatment was not long-lasting as almost all patients (14/15) relapsed including 9 around 3 months post-treatment. An interesting finding was that most of the patients who relapsed responded to their previous failed b/tsDMARDs. Two patients were treated with BCMA×CD3 bispecific T-cell engager, Teclistamab. Thus, the authors introduced the concept of “immune dimming” as opposed to “immune reset” which was a buzzword at the congress to describe transient attenuation of pathogenic immune activity without complete immune ablation.

Can we improve durability of BiTE? 

Teclistamab, a BCMA×CD3 bispecific T-cell engager was evaluated as rescue therapy in 16 patients with severe and refractory RMDs (SSc=2; RA=2; IIM=2; IgG4-RD=2; SjD=1 and Grave’s disease=1) (OP078). The rationale is based on targeting BCMA-expressing plasma cells, which are major producers of pathogenic autoantibodies and are often resistant to anti-CD20 monoclonal antibodies. After a single treatment course, 15/16 of patients achieved clinical responses with 9 achieved drug-free remission with a median ongoing response duration of 11 months (range 8–15). Four patients relapsed (median 5 months) and two were retreated with Teclistamab and responded. In terms of safety, cytokine release syndrome (CRS) occurred in 13/16 patients (i.e. no CRS> grade 2) and all resolved after a dose of tocilizumab. All patients developed hypogammaglobulinaemia and required immunoglobulin replacement (median 2 infusions). 

Two’s company, three’s a crowd! 

In the Late-Breaking Abstract session, data pertaining to early efficacy and safety of CC312, a novel CD19xCD3xCD28 Tri-Specific T-Cell Engager (TriTE) were presented in 12 patients with severe and refractory systemic lupus erythematosus (SLE) including active lupus nephritis (LB0004). CD28 is added to CD19xCD3 to provide co-stimulation, enhancing T-cell activation while potentially reducing T-cell exhaustion. SRI-4 was achieved in 8/8 (100%) and 5/6 (83%) of patients with available follow-up at Weeks 24 and 36 respectively. Two patients who reached WK52 still had sustained response. Deep B-cell depletion was observed, while safety remained favourable, with no immune effector cell-associated neurotoxicity syndrome (ICANS) and no grade ≥2 CRS reported in the dose ranges studied.  

In summary, blinatumomab demonstrated that transient “immune dimming” can reverse refractory RA, although durability remains limited. Teclistamab extended the concept to plasma-cell targeting, offering a potential rescue option for severe RMDs but longer-term data particularly IgG level and infection is of paramount. The tri-specific agent, CC312 introduced a next-generation approach designed to enhance T-cell fitness and achieve deeper, more sustained immune reprogramming. Collectively, these studies suggest that BiTE and TriTE may emerge as off-the-shelf alternatives to cellular therapies, bridging the gap between conventional biologics and CAR-T–based therapies. 

Randomised controlled studies with longer-term data, as well as cost-effectiveness analysis, is now needed.