title: Considerations for non-clinical safety studies of therapeutic peptide vaccines.
abstract: Guidelines for non-clinical studies of prophylactic vaccines against infectious diseases have been published widely, but similar guidelines for therapeutic vaccines, and especially therapeutic peptide vaccines, have yet to be established. The approach to non-clinical safety studies required for therapeutic vaccines differs from that for prophylactic vaccines due to differences in the risk-benefit balance and the mechanisms of action. We propose the following guidelines for non-clinical safety studies for therapeutic peptide vaccines. (i) Since the main safety concern is related to the immune response that might occur at normal sites that express a target antigen, identification of these possible target sites using in silico human expression data is important. (ii) Due to the strong dependence on HLA, it is not feasible to replicate immune responses in animals. Thus, the required non-clinical safety studies are characterized as those detecting off-target toxicity rather than on-target toxicity.
authors.affiliation: Review Division, Pharmaceuticals & Medical Devices Agency (PMDA), Kasumigaseki 3-3-2, Chiyoda-ku, Tokyo 100-0013, Japan. Electronic address: matsumoto-mineo@pmda.go.jp.
authors.forename: Mineo
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: Pre-Clinical Development, GlaxoSmithKline K.K., Sendagaya 4-6-15, Shibuya-ku, Tokyo 151-8566, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Komatsu
authors.affiliation: Research & Development, Sanofi K.K., Nishi Shinjuku 3-20-2, Shinjuku-ku, Tokyo 163-1488, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Tsuchimoto
authors.affiliation: Pathology Department, The Chemo-Sero-Therapeutic Research Institute, Kyokushi Kawabe 1314-1, Kikuchi-shi, Kumamoto 869-1298, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Matsui
authors.affiliation: Research Division, Chugai Pharmaceutical Co. Ltd., Komakado, 1-135, Gotemba, Shizuoka 412-8513, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Global Regulatory Affairs Department, Shionogi Co. Ltd., Shibuya 2-17-5, Shibuya-ku, Tokyo 150-8673, Japan.
authors.forename: Kazuichi
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Review Division, Pharmaceuticals & Medical Devices Agency (PMDA), Kasumigaseki 3-3-2, Chiyoda-ku, Tokyo 100-0013, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Amakasu
authors.affiliation: Review Division, Pharmaceuticals & Medical Devices Agency (PMDA), Kasumigaseki 3-3-2, Chiyoda-ku, Tokyo 100-0013, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Ito
authors.affiliation: Review Division, Pharmaceuticals & Medical Devices Agency (PMDA), Kasumigaseki 3-3-2, Chiyoda-ku, Tokyo 100-0013, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Fueki
authors.affiliation: Review Division, Pharmaceuticals & Medical Devices Agency (PMDA), Kasumigaseki 3-3-2, Chiyoda-ku, Tokyo 100-0013, Japan.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Sawada
authors.affiliation: Review Division, Pharmaceuticals & Medical Devices Agency (PMDA), Kasumigaseki 3-3-2, Chiyoda-ku, Tokyo 100-0013, Japan.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Maki
authors.affiliation: Review Division, Pharmaceuticals & Medical Devices Agency (PMDA), Kasumigaseki 3-3-2, Chiyoda-ku, Tokyo 100-0013, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Onodera
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D003198:Computer Simulation; D015195:Drug Design; D017408:Guidelines as Topic; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D013045:Species Specificity; D022223:Vaccines, Subunit / Q000627:therapeutic use / Q000633:toxicity*
chemical_list: D000941:Antigens; D006680:HLA Antigens; D022223:Vaccines, Subunit
keywords: Cellular immunity; Cytotoxic T-cells (CTLs); Guidelines; Human leukocyte antigen (HLA); Non-clinical safety study; Off-target toxicity; On-target toxicity; Prophylactic vaccines against infectious diseases; Therapeutic peptide vaccines