title: Vaccination with NY-ESO-1 overlapping peptides mixed with Picibanil OK-432 and montanide ISA-51 in patients with cancers expressing the NY-ESO-1 antigen.
abstract: We conducted a clinical trial of an NY-ESO-1 cancer vaccine using 4 synthetic overlapping long peptides (OLP; peptides #1, 79-108; #2, 100-129; #3, 121-150; and #4, 142-173) that include a highly immunogenic region of the NY-ESO-1 molecule. Nine patients were immunized with 0.25 mg each of three 30-mer and a 32-mer long NY-ESO-1 OLP mixed with 0.2 KE Picibanil OK-432 and 1.25 mL Montanide ISA-51. The primary endpoints of this study were safety and NY-ESO-1 immune responses. Five to 18 injections of the NY-ESO-1 OLP vaccine were well tolerated. Vaccine-related adverse events observed were fever and injection site reaction (grade 1 and 2). Two patients showed stable disease after vaccination. An NY-ESO-1-specific humoral immune response was observed in all patients and an antibody against peptide #3 (121-150) was detected firstly and strongly after vaccination. NY-ESO-1 CD4 and CD8 T-cell responses were elicited in these patients and their epitopes were identified. Using a multifunctional cytokine assay, the number of single or double cytokine-producing cells was increased in NY-ESO-1-specific CD4 and CD8 T cells after vaccination. Multiple cytokine-producing cells were observed in PD-1 (-) and PD-1 (+) CD4 T cells. In conclusion, our study indicated that the NY-ESO-1 OLP vaccine mixed with Picibanil OK-432 and Montanide ISA-51 was well tolerated and elicited NY-ESO-1-specific humoral and CD4 and CD8 T-cell responses in immunized patients.
authors: *Department of Gastroenterological Surgery, Graduate School of Medicine ‡‡Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita, Osaka †Department of Respiratory Medicine, Kawasaki Medical School ∥∥Faculty of Health and Welfare, Kawasaki University of Medical Welfare, Kurashiki Departments of ∥Medicine ¶Dermatology #Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Okayama Departments of ‡Immunotherapeutics **Gastrointestinal Surgery, University of Tokyo Hospital, Bunkyo-ku §Department of Pathology, Tokyo Medical University, Shinjuku-ku ††Department of Gastroenterological Surgery, The Cancer Institute Hospital, Koto-ku, Tokyo, Japan §§Ludwig Institute for Cancer Research, New York, NY.
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authors: Nakayama
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000276:immunology* / Q000628:therapy*; D005260:Female; D006801:Humans; D056724:Immunity, Humoral / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000031:analogs & derivatives; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009829:Oleic Acids / Q000008:administration & dosage; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000235:genetics / Q000378:metabolism*; D010844:Picibanil / Q000008:administration & dosage; D016896:Treatment Outcome; D014611:Vaccination; D022223:Vaccines, Subunit / Q000008:administration & dosage* / Q000009:adverse effects / Q000138:chemical synthesis
chemical_list: D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D008565:Membrane Proteins; D009829:Oleic Acids; D010446:Peptide Fragments; D022223:Vaccines, Subunit; C477385:montanide ISA 51; D010844:Picibanil; D008353:Mannitol