Article

NY-ESO-1 is highly expressed in poor-prognosis multiple myeloma and induces spontaneous humoral and cellular immune responses

University of Arkansas at Little Rock, Little Rock, Arkansas, United States
Blood (Impact Factor: 10.43). 06/2005; 105(10):3939-44. DOI: 10.1182/blood-2004-09-3707
Source: PubMed

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.

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    • "ª 2012 Blackwell Publishing Ltd British Journal of Haematology, 2012, 158, 700–711 research paper broad range of cellular and humoral immune responses. In myeloma, several reports have described sporadic overexpression of CTA and accompanying CTA-specific T cell and B cell responses (Lim et al, 2001; Wang et al, 2003; Jungbluth et al, 2005; Van Rhee et al, 2005; Condomines et al, 2007). Induced CTA alloreactivity has also been reported in MM patients undergoing allografting, possibly associated with freedom from relapse (Atanackovic et al, 2007). "
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    British Journal of Haematology 07/2012; 158(6):700-11. DOI:10.1111/j.1365-2141.2012.09225.x · 4.96 Impact Factor
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    • "NY-ESO-specific CTLs generated from patients with MM were shown to kill primary myeloma cells, normal cells pulsed with a NY-ESO-1 peptide, but not normal cells pulsed with an irrelevant peptide. Spontaneous humoral and CD8− T cell-mediated responses to NY-ESO-1 have been identified in patients with advanced disease [99] [124] [126]. Vaccination strategies targeting NY-ESO-1 may be effective at inducing specific antimyeloma immunity, and a clinical trial evaluating the efficacy of an NY-ESO peptide vaccination given in conjunction with GM-CSF is underway [99]. "
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    Clinical and Developmental Immunology 05/2012; 2012:753407. DOI:10.1155/2012/753407 · 2.93 Impact Factor
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    • "Spontaneous antibodies and T lymphocytes directed against NY-ESO-1 were detected in MM patients. After being expanded by autologous antigen presenting cells (APCs) pulsed with NY-ESO-1-derived peptide analog, the specific CTLs were able to lyse primary MM cells [54]. Ropporin is a novel CTA identified in 2007 [34]. "
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