Heinz-Kurt Hochkeppel

Treatment of anti-recombinant interferon-alpha 2 antibody positive CML patients with natural interferon-alpha

Summary Of 38 patients with a Philadelphia‐chromosome positive chronic myeloid leukaemia treated with recombinant interferon alpha (rIFN‐α) 2a or 2b and monitored for emergence of IFN‐antibodies in their sera 11 patients developed rIFN‐α2 binding and 10 rIFN‐α2 neutralizing antibodies. rIFN‐α neutralizing antibody positive patients experienced significantly (P<0·025) more clinical relapses (6/10) than IFN‐antibody negative patients (6/28) during continuous IFN‐therapy. Furthermore, IFN‐antibody‐positive patients with titre above 400 INU/ml were more likely to relapse under rIFN‐α‐therapy than IFN‐antibody‐negative patients with titre below 400 INU/ml (P<0·05).

IFN-τ Exhibits Potent Suppression of Human Papillomavirus E6/E7 Oncoprotein Expression

The effects of interferon-tau (IFN-tau) on tumor suppressor factors and virus oncoprotein expression were compared with two other type I IFN in human papillomavirus (HPV-16)-transformed cells. Nontumorigenic human keratinocytes, HuKc/HPV-16d-2C (d-2C), treated with recombinant human IFN-alpha2a (Roferon), a human recombinant alpha IFN hybrid, alpha B/D (IFN-alphaB/D), or ovine IFN-tau were evaluated for their effects on the levels of E6 and E7 expression. IFN-tau was comparable to IFN-alpha2a in decreasing intracellular levels of E6 and E7, and IFN-alphaB/D was more effective than IFN-a2a in suppressing E7 levels. All three IFN were capable of increasing the cellular concentration of wild-type p53 tumor suppressor with the magnitude IFN-tau > IFN-alpha2a > IFN-alphaB/D. Increases in p53 concentrations correlated with the observed decreases in E6 mRNA and protein levels. The antiviral effects observed in this study reveal that IFN-tau has potent antipapillomavirus activity. Sequences/structures unique to IFN-tau could allow for alternative IFN/receptor interactions and may explain the differences in biologic function.