Oromucosal interferon therapy: marked antiviral and antitumor activity.
Oromucosal administration of murine interferon-alpha/beta (IFN-alpha/beta) or individual recombinant species of murine IFN-alpha, IFN-beta, or IFN-gamma or recombinant human IFN-alpha1-8, which is active in the mouse, exerted a marked antiviral activity in mice challenged systemically with a lethal dose of encephalomyocarditis virus (EMCV), vesicular stomatitis virus (VSV), or varicella zoster virus (VZV). The effects observed were dose dependent and similar in magnitude to those observed following parenteral administration of the same dose of IFN. No antiviral activity was observed after oromucosal administration of murine IFN-alpha/beta in animals in which the IFN receptor had been inactivated by homologous recombination. In contrast to parenteral treatment, oromucosal IFN therapy was found to be ineffective when IFNs were administered before virus infection. Oromucosal administration of IFN-alpha also exerted a marked antitumor activity in mice injected i.v. with highly malignant Friend erythroleukemia cells or other transplantable tumors, such as L1210 leukemia, which has no known viral etiology, the EL4 tumor, or the highly metastatic B16 melanoma. These results show that high doses of IFN can be administered by the oromucosal route apparently without ill effect, raising the possibility that the oromucosal route will prove to be an effective means of administering high doses of IFN that are clinically effective but poorly tolerated.
Tovey
M G
MG
Laboratory of Viral Oncology, UPR 9045 CNRS, Institut de Recherches sur le Cancer/IFR Y1221, Villejuif, France. tovey@infobiogen.fr
Maury
C
C
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D004686:Encephalomyocarditis virus / Q000472:pathogenicity; D005260:Female; D005622:Friend murine leukemia virus / Q000472:pathogenicity; D014645:Herpesvirus 3, Human / Q000472:pathogenicity; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use*; D007928:Lethal Dose 50; D007942:Leukemia, Experimental / Q000188:drug therapy; D008297:Male; D051379:Mice; D009061:Mouth Mucosa; D009374:Neoplasms, Experimental / Q000188:drug therapy; D011994:Recombinant Proteins / Q000627:therapeutic use; D014407:Tumor Cells, Cultured; D014721:Vesicular stomatitis Indiana virus / Q000472:pathogenicity
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D007370:Interferon Type I; D011994:Recombinant Proteins