TCR T cells targeting IgA- and IgG-expressing multiple myeloma - PubMed
3 hours ago
- #TCR T cells
- #multiple myeloma
- #immunotherapy
- TCR T cells targeting IgA- and IgG-expressing multiple myeloma show promise in treating the disease.
- The constant domains of the immunoglobulin heavy chain (IgH) are identified as novel targets for therapeutic T cell receptors (TCRs).
- IGH expression is high and homogeneous in over 95% of multiple myeloma (MM) patients.
- Peptides from IgA and IgG constant regions were eluted from HLA-A*02:01, and reactive TCRs were isolated from healthy donors.
- Engineered T cells with TCRs specific for IgA or IgG selectively eliminated MM cells in vitro from 20 HLA-A*02:01+ patients.
- In vivo, IgA-TCR T cells eradicated IgA+HLA-A*02:01+ MM cells in xenograft models and reduced circulating IgA in humanized mice.
- This approach could make ~40% of patients of European descent eligible for TCR T cell therapy and may be applicable to lymphoma and autoimmune diseases.