caa a22 4500 477127185 CHVBK 20180405111653.0 cr unu---uuuuu 170330e19971001xx s 000 0 eng 10.1023/A:1012193326789 doi (NATIONALLICENCE)springer-10.1023/A:1012193326789 Protein Aggregates Seem to Play a Key Role Among the Parameters Influencing the Antigenicity of Interferon Alpha (IFN-α) in Normal and Transgenic Mice [Elektronische Daten] [Andrea Braun, Lia Kwee, Mark Labow, Jochem Alsenz] Purpose. During long-term treatment of various malignant or viral diseases with IFN-α up to 20% of patients develop anti-IFN-α antibodies for as yet unknown reasons. Methods. To address this issue, a mouse model using Balb/C mice was established and the relevance of several potentially anti-IFN-α antibodies inducing factors was studied. Results. The model revealed that both a higher frequency of injections and a higher dosage of IFN-α were more immunogenic and that the route of administration affected the antibody response to IFN-α. The intrinsic immunostimulatory activity of IFN-α itself also enhanced the immune response. IFN-α protein aggregates (IFN-α-IFN-α and human serum albumin (HSA)-IFN-α aggregates), which were recently identified in all marketed IFN-α products, were significantly more immunogenic than IFN-α monomers. These aggregates broke the tolerance against human IFN-α monomers in human IFN-α transgenic mice. Conclusions. Based on these animal studies it is proposed that the immune response to IFN-α in humans is most probably elicited by a combination of several factors among which IFN-α protein aggregates seem to play a key role. Plenum Publishing Corporation, 1997 interferon alpha (IFN-α) nationallicence animal model (mouse) nationallicence antigenicity nationallicence protein aggregates nationallicence route of administration nationallicence dosage regimen nationallicence immunomodulation nationallicence Braun Andrea Preclinical Research Department, Pharma Division, F. Hoffmann-La Roche Ltd, Grenzacherstrasse, CH-4002, Basel, Switzerland aut Kwee Lia Department of Biotechnology, F. Hoffmann-La Roche Ltd, Nutley, New Jersey aut Labow Mark Department of Biotechnology, F. Hoffmann-La Roche Ltd, Nutley, New Jersey aut Alsenz Jochem Preclinical Research Department, Pharma Division, F. Hoffmann-La Roche Ltd, Grenzacherstrasse, CH-4002, Basel, Switzerland aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/10(1997-10-01), 1472-1478 0724-8741 14:10<1472 1997 14 11095 https://doi.org/10.1023/A:1012193326789 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012193326789 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Braun Andrea Preclinical Research Department, Pharma Division, F. Hoffmann-La Roche Ltd, Grenzacherstrasse, CH-4002, Basel, Switzerland aut NATIONALLICENCE 700 1- Kwee Lia Department of Biotechnology, F. Hoffmann-La Roche Ltd, Nutley, New Jersey aut NATIONALLICENCE 700 1- Labow Mark Department of Biotechnology, F. Hoffmann-La Roche Ltd, Nutley, New Jersey aut NATIONALLICENCE 700 1- Alsenz Jochem Preclinical Research Department, Pharma Division, F. Hoffmann-La Roche Ltd, Grenzacherstrasse, CH-4002, Basel, Switzerland aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/10(1997-10-01), 1472-1478 0724-8741 14:10<1472 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer