Interferon alfa-2a (Roferon@-A, Hoffmann-La Roche Inc., Nutley, NJ) is identical to one of approximately 15 subtypes of interferon alpha made by human leukocytes and is produced in bacteria using recombinant DNA techniques. In its antiviral, antiproliferative, and immunomodulatory activities it is similar to leukocyte interferon alpha. These activities are species-restricted and have been demonstrable, thus far, only in humans, certain other primates, bovines, and guinea pigs or cells derived therefrom. The possibility that the toxicity of interferon alfa-2a would also be species-restricted appears to have been confirmed by results obtained thus far. Toxicological studies in rats, mice and several species of monkeys have failed to indicate the side effects that have been observed in humans. However, studies in species in which interferon alfa-2a is active and in others in which it is not, have revealed similar pharmacokinetics and elimination mechanisms.
Cancer 571648-1656,1986.
EFORE their production by recombinant DNA tech-B niques, the human alpha-interferons were available for preclinical and clinical evaluation only as impure preparations containing a mixture of closely related, but different, proteins now known as subtypes. The early interferons were made by viral infection of human leukocytes cultured in vitro, and were purified for clinical trial to approximately 1% purity.' Recombinant DNA techniques have led not only to the production of interferons free from other substances such as lymphokines produced by the cultured lymphocytes, but also to the production of individual molecular species free from other subtypes. Interferon alfa-2a (Roferon@-A, Hoffmann-La Roche Inc., Nutley, NJ) is one of more than 15 such subtypes that have been cloned thus far.* An early task in the preclinical development of interferon alfa-2a was, therefore, to compare its biologic properties with those of the partially purified leukocyte interferons used earlier. This task was complicated by the biologic property shared to some degree by all interferons: their species-restricted a~tivity.~ Consequently, the preclinical testing of interferon alfa-2a had to be carried out in human cell cultures in vitro, with human tumors grown in nude mice or in certain species of monkeys. After clinical trials had been initiated, it was discovered that interferon alfa-2a is also active in guinea pigs.4 It thus became possible to obtain data on the efficacy of interferon alfa-2a against herpes simplex virus infections in that species.