IN-VIVO PROPERTIES OF AN IGG3-IL-2 FUSION PROTEIN - A GENERAL STRATEGY FOR IMMUNE POTENTIATION

In this report, we describe a strategy for enhancing the immunogenicit y of a wide variety of Ags by linking them to IL-2 via an lgG3-IL-2 fu sion protein with high affinity for a convenient hapten Ag, dansyl (DN S; N,N-dimethyl-1-aminonaphthalene-5-sulfonyl chloride), This fusion p rotein, anti-DNS-lgG3-IL-2, combines the functional characteristics of its constituents and has pharmacokinetic properties that are greatly improved over those of IL-2 and a previously described IgCI-IL-2 fusio n. The molecule is intact and recoverable from the blood of mice hours after i.p. injection and reaches distant organs throughout the animal . The 7-h in vive half-life of this molecule is much longer than that of IL-2, addressing a major obstacle in the application of IL-2 to hum an diseases, including cancer and AIDS. Additionally, the Ab's specifi city for the hapten dansyl and the convenient chemistry of dansyl prov ide a means to link IL-2 to virtually any molecule of interest without the complexities and uncertainties of making IL-2 fusions with each m olecule individually. Using hapten-conjugated-BSA (DNS-BSA) as a model Ag we show that the Ab response elicited by anti-DNS-IgC3-IL-2-bound DNS-BSA-Sepharose injected into mice is increased over that of DNS-BSA -Sepharose or anti-DNS-IgG3-bound DNS-BSA-Sepharose. Anti-DNS-IgC3-IL- 2 also increased the Ab response to soluble DNS-BSA after a booster in jection. This system should be useful in testing the ability of IL-2 t o potentiate the immune response to Ag and in screening a large number of potential Ags for use in vaccines, The dramatically improved pharm acokinetics should also overcome one of the major difficulties in appl ying IL-2 to the treatment of human disease, its short half-life.