In the early 1990s, it was realised that complexing cytokines with anticytokine mAbs could prolong the half-life of the cytokine in serum [65]. Such bound cytokines could maintain their in vivo activity for a couple of days compared with just a few minutes for free cytokine alone. Prolonging cytokine half-life with mAbs applied to several cytokines, including IL-2 [66,67]. In this respect, the administration of IL-2/anti-IL-2 mAb complexes proved beneficial for tumour immunotherapy, although this effect was limited to a mild increase in NK cell-mediated tumour rejection.
Recently, it has been found that the combination of recombinant IL-2 with certain anti-IL-2 mAb leads to massive proliferation of antigen-primed (memory) CD8+ T cells and also NK cells [22]. In contrast to these ‘stimulatory’ mAbs, other anti-IL-2 mAbs combined with recombinant IL-2 did not stimulate memory CD8+ T cells and NK cells, but instead led to a three- to fourfold expansion of CD4+ CD25+ Tregs. The authors refer to these latter anti-IL-2 mAbs as ‘inhibitory’ mAbs.
5.1 Stimulatory antibodies