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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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Submitted September 29, 2004
Accepted December 17, 2004
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 J Tricot
Myeloma Institute for Research and Therapy, Section of Gene and Immunotherapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA
Department of Surgery, University of Basel, Basel, Switzerland
* Corresponding author; email: vanrheefrits{at}uams.edu.
The presence of abnormal metaphase cytogenetics (CA) is the key negative predictor of outcome in multiple myeloma (MM). Gene expression profiling (GEP) of such patients showed increased expression of NY-ESO-1 compared to patients with normal cytogenetics (60% vs. 31%, P=0.004). NY-ESO-1 was also highly expressed in relapsing MM especially those with CA (100% vs. 60.7%, P< 0.0001). 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 ELISA in 33% of patients with NY-ESO-1 positive MM, especially in CA patients (9/13;70%), but in none of the NY-ESO-1 negative MM patients (n=27) or normal donors (n=21). Spontaneous NY-ESO-1157-165 specific T-cells (0.2% to 0.6% of CD8+ T-cells) were found in the peripheral blood of NY-ESO-1 positive 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, ET 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 upon NY-ESO-1 peptide stimulation and is functionally active. NY-ESO-1 should therefore be an ideal tumor target antigen for immunotherapy of poor prognosis MM.
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