We conducted a phase I clinical trial of a cancer vaccine using a 20-mer NY-ESO-1f peptide (NY-ESO-1 91-110) that includes multiple epitopes recognized by antibodies, and CD4 and CD8 T cells. Ten patients were immunized with 600 lg of NY-ESO-1f peptide mixed with 0.2 KE Picibanil OK-432 and 1.25 ml Montanide ISA-51. Primary end points of the study were safety and immune response. Subcutaneous injection of the NY-ESO-1f peptide vaccine was well tolerated. Vaccine-related adverse events observed were fever (Grade 1), injection-site reaction (Grade 1 or 2) and induration (Grade 2). Vaccination with the NY-ESO-1f peptide resulted in an increase or induction of NY-ESO-1 antibody responses in nine of ten patients. The sera reacted with recombinant NY-ESO-1 whole protein as well as the NY-ESO-1f peptide. An increase in CD4 and CD8 T cell responses was observed in nine of ten patients. Vaccine-induced CD4 and CD8 T cells responded to NY-ESO-1 91-108 in all patients with various HLA types with a less frequent response to neighboring peptides. The findings indicate that the 20-mer NY-ESO-1f peptide includes multiple epitopes recognized by CD4 and CD8 T cells with distinct specificity. Of ten patients, two with lung cancer and one with esophageal cancer showed stable disease. Our study shows that the NY-ESO-1f peptide vaccine was well tolerated and elicited humoral, CD4 and CD8 T cell responses in immunized patients.The NY-ESO-1 antigen was originally identified in esophageal cancer by serological expression cloning (SEREX) using autologous patient serum.1,2 NY-ESO-1 expression is observed in a wide range of human malignancies, 3,4 but the expression is restricted to germ cells in the testes in normal adult tissues.
1,3Therefore, NY-ESO-1 has emerged as a prototype of a class of cancer/testis (CT) antigens.
5More than 100 patients with NY-ESO-1-expressing tumors have received the NY-ESO-1 vaccine either as fulllength recombinant protein given as protein alone, with ISCOMATRIX V R or cholesterol-bearing hydrophobized pullulan (CHP), delivered in a recombinant vaccinia or fowlpox vector, or as the NY-ESO-1b peptide given with various adjuvants. [6][7][8][9][10][11] These studies established safety with various preparations of the NY-ESO-1 vaccine, showing toxicity to be limited to Grade 1 or 2 injection-site reactions or flu-like