Safety Study of NY-ESO-1 Protein Vaccine to Treat Cancer Expressing NY-ESO-1

The purpose of this study is to assess the safety of repeated doses of cholesterol-bearing hydrophobized pullulan (CHP) and NY-ESO-1 protein (CHP-NY-ESO-1) and describe the NY-ESO-1 specific-humoral and cellular immune response to immunization with CHP-NY-ESO-1 in patients with cancer expressing NY-ESO-1.

NY-ESO-1 was isolated by serological analysis of recombinant cDNA expression libraries (SEREX), using tumor mRNA and autologous serum from an esophageal cancer patient. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that NY-ESO-1 displayed the typical expression pattern of CT antigens. NY-ESO-1 mRNA was expressed only in testis of normal tissues tested and in various types of cancer, including lung cancer, breast cancer, malignant melanoma and bladder cancer. LAGE-1 was identified by the representational difference analysis and revealed to display 84% amino acid homology with NY-ESO-1. In most cases, expression of LAGE-1 parallels the expression of NY-ESO-1. Since testis is an immune privileged organ where HLA molecules are not expressed, these antigens can be considered tumor-specific.

Because of frequent NY-ESO-1 mRNA expression and high immunogenicity in advanced cancer, NY-ESO-1 is an attractive target molecule for a cancer vaccine. Current therapies against advanced cancer have limited effectiveness. The idea of vaccination with NY-ESO-1 protein in cancer patients with tumors expressing NY-ESO-1 mRNA is based on two findings: 1) the number of CD8+ T cell epitopes identified in NY-ESO-1 molecule are limited to those binding to HLA-A0201, A31, Cw3 and Cw6. These HLA subtypes are carried by a minor Japanese population; 2) CD8+ T cell responses specific to NY-ESO-1 are polyclonal. Protein vaccination may induce immune response more effectively against tumors expressing NY-ESO-1 than peptide immunization.

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Inclusion Criteria:

• Histologically proven cancer
• Confirmed NY-ESO-1 expression
• No other effective therapy available
• 4 weeks since conventional therapy before start of the current protocol
• Performance status < 2 (ECOG scale)
• Age > 18
• Able and willing to give written informed consent

Exclusion Criteria:

• Serious illness
• Metastatic diseases to central nervous system
• Concomitant systemic treatment with corticosteroids, anti-histaminic drugs or NSAIDs
• HIV positive
• Mental impairment that may compromise the ability to give written informed consent
• Pregnancy and breastfeeding