title: An in vitro human cell-based assay to rank the relative immunogenicity of proteins.
abstract: A method to rank proteins based on their relative immunogenicity has been devised. A statistical analysis of peptide-specific responses in large human donor pools provides a structure index value metric that ranked four industrial enzymes in the order determined by both mouse and guinea pig exposure models. The ranking method also compared favorably with human sensitization rates measured in occupationally exposed workers. Structure index values for other proteins known to cause immune responses in humans were also determined and found to be higher than the value determined for human beta2-microglobulin. Using values from known immunogenic and putative nonimmunogenic proteins, a cut-off value was established. The structure index value calculation provides a comparative method to predict subsequent immunogenicity on a human population basis without the need to use animal models. Information provided by this assay can be used in the early development of protein therapies and other protein-based applications to select or create reduced immunogenicity variants.
authors.affiliation: Genencor International, Palo Alto, California 94304, USA.
authors.forename: Marcia
authors.initials: M
authors.lastname: Stickler
authors.forename: Narapon
authors.initials: N
authors.lastname: Rochanayon
authors.forename: O Jennifer
authors.initials: OJ
authors.lastname: Razo
authors.forename: Jeanette
authors.initials: J
authors.lastname: Mucha
authors.forename: Wendy
authors.initials: W
authors.lastname: Gebel
authors.forename: Nargol
authors.initials: N
authors.lastname: Faravashi
authors.forename: Regina
authors.initials: R
authors.lastname: Chin
authors.forename: Susan
authors.initials: S
authors.lastname: Holmes
authors.forename: Fiona A
authors.initials: FA
authors.lastname: Harding
mesh_terms: D000485:Allergens / Q000276:immunology*; D001681:Biological Assay; D001782:Blood Donors; D015496:CD4-Positive T-Lymphocytes; D002478:Cells, Cultured; D003713:Dendritic Cells; D005512:Food Hypersensitivity / Q000209:etiology*; D006680:HLA Antigens; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D010455:Peptides / Q000276:immunology*; D011506:Proteins / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000209:etiology*; D013381:Subtilisins / Q000276:immunology
chemical_list: D000485:Allergens; D006680:HLA Antigens; D016056:Immunodominant Epitopes; D010455:Peptides; D011506:Proteins; D013381:Subtilisins