title: NY-ESO-1 is highly expressed in poor-prognosis multiple myeloma and induces spontaneous humoral and cellular immune responses.
abstract: The presence of a metaphase cytogenetic abnormality (CA) is the key negative predictor of outcome in patients with multiple myeloma (MM). Gene expression profiling (GEP) of such patients showed increased expression of NY-ESO-1 compared to patients with normal cytogenetics (60% versus 31%; P = .004). NY-ESO-1 was also highly expressed in relapsing MM especially patients with CA (100% versus 60.7%; P < .001). GEP findings were confirmed at the protein level by immunostaining of marrow biopsies for NY-ESO-1. We detected spontaneous NY-ESO-1-specific antibodies by enzyme-linked immunosorbent assay in 33% of patients with NY-ESO-1+ MM, especially in CA patients (9 of 13; 70%), but in none of the NY-ESO-1- patients with MM (n = 27) or healthy donors (n = 21). Spontaneous NY-ESO-1(157-165)-specific T cells (0.2%-0.6% of CD8+ T cells) were found in the peripheral blood of NY-ESO-1+ MM with HLA-A*0201/NY-ESO-1(157-165) tetramers. These NY-ESO-1-specific T cells, when expanded, killed primary MM cells (50% lysis, effector-target [E/T] ratio, 10:1). Our data demonstrate that NY-ESO-1 is frequently expressed in MM with CA and is capable of eliciting spontaneous humoral and T-cell immunity. The pool of NY-ESO-1-specific cytotoxic T cells expands easily on NY-ESO-1 peptide stimulation and is functionally active. NY-ESO-1 should therefore be an ideal tumor target antigen for immunotherapy of patients with poor-prognosis MM.
authors.affiliation: University of Arkansas for Medical Sciences, Myeloma Institute for Research and Therapy, 4301 West Markham, no. 776, Little Rock, AR 72205, USA. vanrheefrits@uams.edu
authors.forename: Frits
authors.initials: F
authors.lastname: van Rhee
authors.forename: Susann M
authors.initials: SM
authors.lastname: Szmania
authors.forename: Fenghuang
authors.initials: F
authors.lastname: Zhan
authors.forename: Sushil K
authors.initials: SK
authors.lastname: Gupta
authors.forename: Mindy
authors.initials: M
authors.lastname: Pomtree
authors.forename: Pei
authors.initials: P
authors.lastname: Lin
authors.forename: Ramesh B
authors.initials: RB
authors.lastname: Batchu
authors.forename: Amberly
authors.initials: A
authors.lastname: Moreno
authors.forename: Guilio
authors.initials: G
authors.lastname: Spagnoli
authors.forename: John
authors.initials: J
authors.lastname: Shaughnessy
authors.forename: Guido
authors.initials: G
authors.lastname: Tricot
mesh_terms: D000906:Antibodies / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism*; D001706:Biopsy; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D009101:Multiple Myeloma / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D012008:Recurrence; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D008565:Membrane Proteins