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Pharm Res. 1997 Oct;14(10):1472-8.

Protein aggregates seem to play a key role among the parameters influencing the antigenicity of interferon alpha (IFN-alpha) in normal and transgenic mice.

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  • 1Preclinical Research Department, F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Abstract

PURPOSE:

During long-term treatment of various malignant or viral diseases with IFN-alpha up to 20% of patients develop anti-IFN-alpha 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-alpha antibodies inducing factors was studied.

RESULTS:

The model revealed that both a higher frequency of injections and a higher dosage of IFN-alpha were more immunogenic and that the route of administration affected the antibody response to IFN-alpha. The intrinsic immunostimulatory activity of IFN-alpha itself also enhanced the immune response. IFN-alpha protein aggregates (IFN-alpha-IFN-alpha and human serum albumin (HSA)-IFN-alpha aggregates), which were recently identified in all marketed IFN-alpha products, were significantly more immunogenic than IFN-alpha monomers. These aggregates broke the tolerance against human IFN-alpha monomers in human IFN-alpha transgenic mice.

CONCLUSIONS:

Based on these animal studies it is proposed that the immune response to IFN-alpha in humans is most probably elicited by a combination of several factors among which IFN-alpha protein aggregates seem to play a key role.

PMID:
9358564
[PubMed - indexed for MEDLINE]
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