The present invention concerns methods and compositions for forming
cytokine-
antibody complexes using dock-and-lock technology. In preferred embodiments, the
cytokine-MAb DNL complex comprises an IgG
antibody attached to two AD (anchor domain) moieties and four cytokines, each attached to a DDD (docking and dimerization domain)
moiety. The DDD moieties form dimers that bind to the AD moieties, resulting in a 2:1 ratio of DDD to AD. The
cytokine-MAb complex exhibits improved
pharmacokinetics, with a significantly longer serum half-life than either naked cytokine or PEGylated cytokine. The cytokine-MAb complex also exhibits significantly improved
in vitro and
in vivo efficacy compared to cytokine alone,
antibody alone, unconjugated cytokine plus antibody or cytokine-MAb DNL complexes incorporating an irrelevant antibody. In more preferred embodiment the cytokine is G-CSF,
erythropoietin or INF-α2b.