title: Phase I trial of a cancer vaccine consisting of 20 mixed peptides in patients with castration-resistant prostate cancer: dose-related immune boosting and suppression.
abstract: The heterogeneity expression of tumor-associated antigens (TAA) and variability of human T cell repertoire suggest that effective cancer vaccine requires induction of a wide breadth of cytotoxic T lymphocyte (CTL) specificities. This can be achieved with vaccines targeting multiple TAA. We evaluated the safety and immune dynamics of a cancer vaccine consisting of 20 mixed peptides (KRM-20) designed to induce CTLs against 12 different TAA in patients with castration-resistant prostate cancer (CRPC). Patients received each of three different randomly assigned doses of KRM-20 (6, 20, or 60 mg) once a week for 6 weeks. KRM-20 was applicable for patients with positive human leukocyte antigen (HLA) A2, A3, A11, A24, A26, A31 or A33 alleles, which cover the majority of the global population. To evaluate the minimum immunological effective dose (MIED), peptide-specific CTL and immunoglobulin G (IgG) responses, and immune suppressive subsets were evaluated during the vaccination. Total of 17 patients was enrolled. No serious adverse drug reactions were encountered. The MIED of KRM-20 in CTL or IgG response calculated by logistic regression model was set as 16 or 1.6 mg, respectively. The frequency of immune suppressive subsets was fewer in the 20 mg cohort than that in 6 or 60 mg cohort. Clinical responses determined by prostate-specific antigen levels were two partial responses (from the 20 mg cohort), five no changes and ten progressive diseases. Twenty milligrams of KRM-20 could be recommended for further studies because of the safety and ability to augment CTL activity.
authors: Division of Clinical Research, Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan, noguchi@med.kurume-u.ac.jp.
authors: Masanori
authors: M
authors: Noguchi
authors: Gaku
authors: G
authors: Arai
authors: Kazumasa
authors: K
authors: Matsumoto
authors: Seiji
authors: S
authors: Naito
authors: Fukuko
authors: F
authors: Moriya
authors: Shigetaka
authors: S
authors: Suekane
authors: Nobukazu
authors: N
authors: Komatsu
authors: Satoko
authors: S
authors: Matsueda
authors: Tetsuro
authors: T
authors: Sasada
authors: Akira
authors: A
authors: Yamada
authors: Tatsuyuki
authors: T
authors: Kakuma
authors: Kyogo
authors: K
authors: Itoh
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000097:blood; D001859:Bone Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D060908:CTLA-4 Antigen / Q000097:blood; D019496:Cancer Vaccines / Q000008:administration & dosage*; D015331:Cohort Studies; D005500:Follow-Up Studies; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010446:Peptide Fragments / Q000276:immunology*; D011379:Prognosis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D060908:CTLA-4 Antigen; D019496:Cancer Vaccines; D006680:HLA Antigens; D007074:Immunoglobulin G; D010446:Peptide Fragments