title: Induction of multiple myeloma-reactive T cells during post-transplantation immunotherapy with donor lymphocytes and recipient DCs.
abstract: Recently, we demonstrated that reduced intensity conditioning (RIC) followed by partial T-cell-depleted SCT creates a platform for inducing the graft-versus-myeloma effect by adjuvant immunotherapy. Here, we evaluated mHA-specific T-cell responses in a multiple myeloma (MM) patient who was treated with RIC-SCT followed by donor lymphocyte infusion (DLI) and subsequent recipient DC vaccination. We isolated a mHA-specific CTL clone with the capacity to target MM tumor cells from this patient experiencing long-term CR. This CTL clone recognizes an HLA-A3-restricted mHA and mediates killing of both primary MM cells and the MM-cell line U266, while BM-derived fibroblasts are not recognized. CTL-specific T-cell receptor (TCR) transcripts could be detected by quantitative PCR analysis in both peripheral blood and BM during tumor remission. Interestingly, a strong increase of CTL-specific TCR transcripts at the BM tumor site was observed following DLI and recipient DC vaccination, while the TCR signal in peripheral blood decreased. These findings illustrate that the approach of partial T-cell-depleted RIC-SCT followed by post-transplantation immunotherapy induces mHA-specific T-cell responses targeting MM tumor cells.
authors.affiliation: Department of Laboratory Medicine-Laboratory of Hematology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Broen
authors.forename: A
authors.initials: A
authors.lastname: Greupink-Draaisma
authors.forename: H
authors.initials: H
authors.lastname: Fredrix
authors.forename: N
authors.initials: N
authors.lastname: Schaap
authors.forename: H
authors.initials: H
authors.lastname: Dolstra
mesh_terms: D000328:Adult; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D020350:Graft vs Tumor Effect / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D009101:Multiple Myeloma / Q000276:immunology* / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology
chemical_list: D011948:Receptors, Antigen, T-Cell