Posted: Wednesday, March 29, 2023
According to Mirjam H.M. Heemskerk, PhD, of Leiden University Medical Center, the Netherlands, T-cell receptor–engineered cells may be valuable in the treatment of multiple myeloma, since they can recognize peptides presented in human leukocyte antigen (HLA) that may be derived from any protein. Therefore, they conducted a study to identify potential immunoglobulin J chain T-cell receptors that targeted epitopes in various HLA cells. These results were published in the Journal of Hematology & Oncology.
“T-cell receptor–transduced CD8 T cells demonstrated stringent specificity for J chain–expressing target cells with the relevant HLA restriction alleles,” the investigators concluded. “Potent eradication of multiple myeloma cells in vitro as well as in vivo demonstrates high promise of J chain T-cell receptor T cells for clinical development as a novel therapy of multiple myeloma.”
J chain expression in multiple myeloma cell lines was measured using quantitative real-time polymerase chain reaction, and J chain–derived epitopes presented by multiple myeloma cells were identified using immunopeptidomics. Peptide-HLA tetramers were generated to isolate J chain–specific T-cell clones from peripheral blood mononuclear cells of HLA-mismatched healthy donors.
T cells specific for J chain peptides that recognized and lysed J chain–positive multiple myeloma cells were identified in HLA-A1, -A3, -A11, and -A24 cell lines. Before being transferred to CD8 T cells, T-cell receptors of the most “promising” T-cell clones were sequenced and cloned into retroviral vectors. When the respective HLA restriction alleles and J chain were expressed, J chain T-cell receptor T cells recognized target cells, but J chain or HLA-negative cells were not recognized.
The study authors also observed that J chain T-cell receptor T cells lysed patient-derived J chain–positive multiple myeloma samples. Additionally, a preclinical in vivo model showed that J chain-A1, -A3, -A11, and -A24 T-cell receptor cells “strongly eradicated” multiple myeloma cells, resulting in a 100-fold lower tumor burden compared with control mice.
Disclosure: For full disclosures of the study authors, visit jhoonline.biomedcentral.com.