title: Novel myeloma-associated antigens revealed in the context of syngeneic hematopoietic stem cell transplantation.
abstract: Targets of curative donor-derived graft-versus-myeloma (GVM) responses after allogeneic hematopoietic stem cell transplantation (HSCT) remain poorly defined, partly because immunity against minor histocompatibility Ags (mHAgs) complicates the elucidation of multiple myeloma (MM)-specific targets. We hypothesized that syngeneic HSCT would facilitate the identification of GVM-associated Ags because donor immune responses in this setting should exclusively target unique tumor Ags in the absence of donor-host genetic disparities. Therefore, in the present study, we investigated the development of tumor immunity in an HLA-A0201(+) MM patient who achieved durable remission after myeloablative syngeneic HSCT. Using high-density protein microarrays to screen post-HSCT plasma, we identified 6 Ags that elicited high-titer (1:5000-1:10 000) Abs that correlated with clinical tumor regression. Two Ags (DAPK2 and PIM1) had enriched expression in primary MM tissues. Both elicited Ab responses in other MM patients after chemotherapy or HSCT (11 and 6 of 32 patients for DAPK2 and PIM1, respectively). The index patient also developed specific CD8(+) T-cell responses to HLA-A2-restricted peptides derived from DAPK2 and PIM1. Peptide-specific T cells recognized HLA-A2(+) MM-derived cell lines and primary MM tumor cells. Coordinated T- and B-cell immunity develops against MM-associated Ags after syngeneic HSCT. DAPK1 and PIM1 are promising target Ags for MM-directed immunotherapy.
authors.affiliation: University of Connecticut School of Medicine, Farmington, CT, USA.
authors.forename: Melinda A
authors.initials: MA
authors.lastname: Biernacki
authors.forename: Yu-tzu
authors.initials: YT
authors.lastname: Tai
authors.forename: Guang Lan
authors.initials: GL
authors.lastname: Zhang
authors.forename: Anselmo
authors.initials: A
authors.lastname: Alonso
authors.forename: Wandi
authors.initials: W
authors.lastname: Zhang
authors.forename: Rao
authors.initials: R
authors.lastname: Prabhala
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Nikhil
authors.initials: N
authors.lastname: Munshi
authors.forename: Donna
authors.initials: D
authors.lastname: Neuberg
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Soiffer
authors.forename: Jerome
authors.initials: J
authors.lastname: Ritz
authors.forename: Edwin P
authors.initials: EP
authors.lastname: Alyea
authors.forename: Vladimir
authors.initials: V
authors.lastname: Brusic
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Wu
mesh_terms: D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D057166:High-Throughput Screening Assays; D006801:Humans; D020014:K562 Cells; D058950:Melanoma-Specific Antigens / Q000097:blood / Q000276:immunology* / Q000302:isolation & purification* / Q000378:metabolism; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000276:immunology / Q000628:therapy*; D040081:Protein Array Analysis; D012074:Remission Induction; D013997:Time Factors; D014185:Transplantation, Isogeneic; D014427:Twins; D054928:Validation Studies as Topic
chemical_list: D058950:Melanoma-Specific Antigens