Interferon immunogenicity: preclinical evaluation of interferon-alpha 2a.
A preclinical evaluation of the immunogenicity of various preparations of interferon-alpha (IFN-alpha) was performed with in vitro and in vivo animal models. The distribution of genes for IFN-alpha 2a, IFN-alpha 2b, and IFN-alpha 2c in various cell populations and the response of human T cell clones to IFN-alpha peptides were investigated. The immunogenicity of IFN-alpha in IFN-alpha 2b transgenic mice and factors that influence the immunogenicity of IFN-alpha in normal mice were also studied. The genes for IFN-alpha 2a and IFN-alpha 2b were found in KG-1 cells, whereas IFN-alpha 2b and IFN-alpha 2c genes were present in Namalwa cells. No difference in proliferation of human T cells, T cell lines, or T cell clones could be obtained with IFN-alpha peptides. In transgenic mice bearing the human IFN-alpha 2b gene, no antibody response was obtained following immunization with either IFN-alpha 2a or IFN-alpha 2b. Normal mice immunized with either IFN-alpha 2a or IFN-alpha 2b produced equivalent titers of antibodies, which cross-reacted with both IFNs. Studies evaluating the relative immunogenicity of IFN-alpha in normal mice demonstrated that a number of treatment and host variables can modulate immunogenicity of IFN-alpha preparations.
Palleroni
A V
AV
Department of Oncology, Hoffmann-La Roche, Inc., Nutley, NJ, USA.
Aglione
A
A
Labow
M
M
Brunda
M J
MJ
Pestka
S
S
Sinigaglia
F
F
Garotta
G
G
Alsenz
J
J
Braun
A
A
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D005796:Genes; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000276:immunology*; D016899:Interferon-beta / Q000276:immunology; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology; D011485:Protein Binding; D011994:Recombinant Proteins; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D010455:Peptides; D011994:Recombinant Proteins; D016899:Interferon-beta