Analysis Of Peripheral And Local Anti-Tumor Immune Response In Esophageal Cancer Patients After Ny-Eso-1 Protein Vaccination

NY-ESO-1 antigen is a prototype of a class of cancer/testis antigens. We carried out a clinical trial using NY-ESO-1 whole protein as a cancer vaccine for 13 advanced cancer patients. We have recently reported that vaccine elicited humoral and cellular immune responses in 9 cancer patients including 4 esophageal cancer patients, and clinical responses were also observed in 4 of 5 evaluable patients. In this study, we analyzed the responses in 8 esophageal cancer patients including 4 newly enrolled patients. Patients were injected subcutaneously at biweekly intervals with NY-ESO-1 recombinant protein formulated with cholesterol-bearing hydrophobized pullulan. Induction of antibody, and CD4 and CD8 T-cell responses were observed in 7, 7 and 6 patients, respectively, out of 8 patients. 1 PR, 2 SD and 2 mixed clinical responses were observed in 6 evaluable patients. No significant adverse events were observed. Furthermore, we analyzed NY-ESO-1 and MHC class I expression and the infiltration of immune cells into tumor samples obtained before and after vaccination from 4 patients by immunohistochemistry. The results showed 2 patients with disappearance of CD4 and CD8 T-cell infiltration, I patient with increase in the number of CD68(+) macrophages and 1 patient with tumor antigen loss in the progressive tumors following vaccinations. The induction of NY-ESO-1 immunity and some preferable clinical outcomes were observed in esophageal cancer patients by vaccination with NY-ESO-1. However. the tumors grew eventually by various mechanisms after vaccination. (C) 2008 Wiley-Liss, Inc.