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Antigen-Specific Immunity in Neuroblastoma Patients

Antibody and T-Cell Recognition of NY-ESO-1 Tumor Antigen¹

Units of Melanoma Genetics [M. R., T. R.], Immunotherapy of Human Tumors [P. D., L. R., G. P., C. C.], Pediatric Oncology [R. L., F. F-B.], Departments of Pathology [P. C.] and Immunohematology and Transfusion Medicine [C. L., F. A.], Istituto Nazionale per lo Studio e la Cura dei Tumori, 20133 Milan, Italy; Ludwig Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, New York 10021 [E. S., L. J. O.]; and Department of Pathology, Cornell University Medical College, New York, New York 10021 [Y-T. C.]

Neuroblastoma cells have been shown to express molecularly defined tumor-associated antigens, which could represent potential targets of T and/or B cell-mediated immunity. However, the existence of a spontaneous immune response to such tumor antigens in neuroblastoma patients has yet to be investigated. In the present work we addressed the issue of whether NY-ESO-1, a germ cell antigen aberrantly expressed in different tumor types, is expressed by neuroblastoma cells and may represent a target for humoral and/or cellular immune responses in neuroblastoma patients. We found that a large fraction of neuroblastoma biopsies, independently from the clinical stage and degree of tumor cell differentiation, expressed significant levels of NY-ESO-1 as assessed by reverse transcription-PCR and immunohistochemistry. NY-ESO-1-specific IgG antibodies were detected in the sera of 10% of neuroblastoma patients with stage III or IV disease, but not in patients in clinical remission or with earlier stages. This suggests that antibody production occurred as a late event in the course of disease. NY-ESO-1-specific immune responses were observed for CD4⁺ and CD8⁺ T cells from peripheral blood lymphocytes in 4 of 8 neuroblastoma patients, as detected by IFN- enzyme-linked immunospot assay after in vitro stimulation either with the NY-ESO-1 recombinant protein or with the HLA-A2-restricted peptide NY-ESO-1_157–167. NY-ESO-1-specific CD4⁺ and CD8⁺ T cells were also able to recognize NY-ESO-1 expressing neuroblastoma cells. The presence of T cells specific for NY-ESO-1 antigen was not associated with the stage of disease, or to the presence or absence of NY-ESO-1 specific antibodies. We conclude that NY-ESO-1 is an immunogenic antigen in neuroblastoma patients and represents a candidate target for immune-based therapy.

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