Bispecific Protein Engager-Armed T Cells (BATs): A Next-Generation Cellular Immunotherapy Platform for Autoimmune Diseases
DOI:
https://doi.org/10.33192/smj.v78i11.285220Keywords:
Autoimmune disease, bispecific protein engager-armed T cells, BATs; bispecific antibodies, CAR-T cells, B cells, plasma cells, immune resetting, cellular immunotherapyAbstract
Autoimmune diseases arise from a loss of immune tolerance, leading to persistent immune-mediated tissue and organ damage. Although the diseases can be controlled by immunosuppressants and biologics, some patients are refractory, relapse after treatment discontinuation, or develop cumulative toxicities. Monoclonal antibodies targeting cytokines, B cells, B-cell activating factor, complement, and interferon pathways mitigate disease conditions but generally require repeated administration and rarely achieve durable treatment-free remission. CD19-directed chimeric antigen receptor (CAR) T cells have demonstrated sustained drug-free remission in some patients with severe refractory autoimmune diseases, providing early evidence that profound B-cell depletion followed by immune reconstitution may induce functional immune resetting. However, CAR-T therapy involves complex manufacturing, genetic modification, high costs, and risks including cytokine-release syndrome, neurotoxicity,
cytopenias, infection, and prolonged hypogammaglobulinemia. Building on our group’s preclinical development of cancer immunotherapies, the Siriraj-developed bispecific protein engager (BiPE)-armed T-cell (BAT) platform could potentially be adapted as a therapeutic strategy for selected autoimmune diseases. CD19-directed BATs could deplete autoreactive B cells, whereas B-cell maturation antigen (BCMA)-directed BATs could target pathogenic antibody-secreting plasma cells. BATs are generated by ex vivo arming of unexpanded polyclonal T cells with BiPEs that bind CD3 and a target-cell antigen, enabling antigen-directed cytotoxicity without genomic modification. This modular platform may provide adaptable, time-limited activity with reduced manufacturing complexity; however, its comparative efficacy, safety, durability, and cost-effectiveness remain to be established clinically. This review critically evaluates the therapeutic rationale, candidate targets and disease indications, current evidence, and key safety, manufacturing, and translational considerations for BAT therapy in autoimmune diseases.
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