Immunoglobulin constant domains as targets for T-cell receptor-based treatment of multiple myeloma.

Immunoglobulin heavy chain constant domains are identified as promising targets for TCR-based therapy in multiple myeloma, with high-avidity T cells recognizing IgG- or IgA-expressing cells.

• Why it matters: Multiple myeloma remains largely incurable despite CAR T-cell advances, and antigen escape limits treatment effectiveness, highlighting the need for alternative targeting strategies.
• What they did: The study used HLA class-I peptidomics to identify nine immunoglobulin-derived peptides presented by common HLA alleles and isolated high-avidity T-cell clones recognizing four of these epitopes, which were tested for specificity and efficacy.
• The result: Immunoglobulin-specific TCR T cells selectively lysed patient-derived MM cells and eradicated tumors in murine models, suggesting potential for targeted immunotherapy that may preserve humoral immunity.