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Blood, 15 May 2005, Vol. 105, No. 10, pp. 3939-3944.
Prepublished online as a Blood First Edition Paper on January 25, 2005; DOI 10.1182/blood-2004-09-3707.
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IMMUNOBIOLOGY
NY-ESO-1 is highly expressed in poor-prognosis multiple myeloma and induces spontaneous humoral and cellular immune responses
Frits van Rhee,
Susann M. Szmania,
Fenghuang Zhan,
Sushil K. Gupta,
Mindy Pomtree,
Pei Lin,
Ramesh B. Batchu,
Amberly Moreno,
Guilio Spagnoli,
John Shaughnessy, and
Guido Tricot
From the Myeloma Institute for Research and Therapy, Section of Gene and Immunotherapy, University of Arkansas for Medical Sciences, Little Rock, AR; and Department of Surgery, University of Basel, Basel, Switzerland.
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-1157-165–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-1157-165 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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