TCR T cells targeting IgA- and IgG-expressing multiple myeloma.

TCR T cells targeting IgA- and IgG-expressing multiple myeloma eliminate HLA-A∗02:01+ MM cells in vitro and in vivo, showing promise for therapy in about 40% of European descent patients.

• Why it matters: Multiple myeloma remains largely incurable despite T-cell therapies, partly because monoclonal immunoglobulins are inaccessible to existing treatments. Targeting the immunoglobulin constant domains could overcome this barrier and expand therapeutic options.
• What they did: Researchers identified peptides from IgA and IgG constant regions, isolated reactive TCRs from healthy donors using allo-HLA-A∗02:01 presentation, and engineered T cells that passed safety screening to target MM cells in vitro and in xenograft models.
• The result: IgA- and IgG-specific TCR T cells selectively eliminated MM cells and reduced circulating immunoglobulins, suggesting that this approach could enable TCR T-cell therapy for a significant subset of MM patients and potentially extend to other diseases.