An in vitro human cell-based assay to rank the relative immunogenicity of proteins.
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.
Stickler
Marcia
M
Genencor International, Palo Alto, California 94304, USA.
Rochanayon
Narapon
N
Razo
O Jennifer
OJ
Mucha
Jeanette
J
Gebel
Wendy
W
Faravashi
Nargol
N
Chin
Regina
R
Holmes
Susan
S
Harding
Fiona A
FA
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
D000485:Allergens; D006680:HLA Antigens; D016056:Immunodominant Epitopes; D010455:Peptides; D011506:Proteins; D013381:Subtilisins