Clinical validation of the "in silico" prediction of immunogenicity of a human recombinant therapeutic protein
Antibodies elicited by protein therapeutics can cause serious side effects in humans. We studied immunogenicity of a recombinant fusion protein (FPX) consisting of two identical, biologically active, peptides attached to human Fc fragment. EpiMatrix, an in silico epitope-mapping tool, predicted prom...
| Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 124(2007), 1 vom: 01. Juli, Seite 26-32 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , , , , , , , , |
| Format: | Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2007
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| Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
| Schlagworte: | Comparative Study Evaluation Study Journal Article Validation Study Epitopes, T-Lymphocyte Immunodominant Epitopes Recombinant Fusion Proteins |
| Zusammenfassung: | Antibodies elicited by protein therapeutics can cause serious side effects in humans. We studied immunogenicity of a recombinant fusion protein (FPX) consisting of two identical, biologically active, peptides attached to human Fc fragment. EpiMatrix, an in silico epitope-mapping tool, predicted promiscuous T-cell epitope(s) within the 14-amino-acid carboxy-terminal region of the peptide portion of FPX. On administration of FPX in 76 healthy human subjects, 37% developed antibodies after a single injection. A memory T-cell response against the above carboxy-terminus of the peptide was observed in antibody-positive but not in antibody-negative subjects. Promiscuity of the predicted T-cell epitope(s) was confirmed by representation of all common HLA alleles in antibody-positive subjects. As predicted by EpiMatrix, HLA haplotype DRB1*0701/1501 was associated with the highest T-cell and antibody response. In conclusion, in silico prediction can be successfully used to identify Class II restricted T-cell epitopes within therapeutic proteins and predict immunogenicity thereof in humans |
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| Beschreibung: | Date Completed 10.08.2007 Date Revised 10.12.2019 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-7035 |