New and modified interferon alfas: preclinical and clinical data.
Recombinant human interferon (IFN)-alpha was the first biotherapeutic agent approved by the US Food and Drug Administration for the treatment of a human malignancy. Its efficacy has also been demonstrated for treatment of several viral diseases. The human genome codes for 12 IFN-alpha proteins, with IFN alpha-1 and IFN alpha-2 accounting for the majority of the naturally occurring IFN-as. However, only subspecies of IFN alpha-2, recombinant human IFN alpha-2a and IFN alpha-2b, are commercially available in the United States. Other species of IFN-a may demonstrate equivalent or improved efficacy and have more tolerable side effects. This article describes ongoing preclinical and clinical studies of several new and modified IFN-alphas. A current phase I trial of a human recombinant IFN alpha-1 is described. Basic pharmacokinetics and clinical studies of polyethylene glycol (PEG) IFN alpha-2b are reviewed as well. Lastly, two novel types of IFN-a, one gene shuffled and one hybridized with human albumin, are summarized.
Masci
Paul
P
Taussig Cancer Center, The Cleveland Clinic Foundation, R35, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Bukowski
Ronald M
RM
Patten
Phillip A
PA
Osborn
Blaire L
BL
Borden
Ernest C
EC
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012709:Serum Albumin / Q000494:pharmacology; D000075462:Serum Albumin, Human
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012709:Serum Albumin; C473631:albuferon; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a; D000075462:Serum Albumin, Human