New therapeutic targets for antibodies and recombinant proteins in organ transplantation

The development of immunosuppressive drugs for tolerance induction or maintenance of an allograft is the key to successful organ transplantation. Humanized mAbs are promising biological agents because of their reduced immunogenicity and favorable bioactivity. Although their clinical application has so far been limited to the anti-CD3 and anti-recombinant IL-2 mAbs, new antibodies have been developed against several targets, including cell-surface molecules involved in T-cell activation, proliferation and trafficking. In addition, developments within the field of bioengineering have allowed for the production of fusion molecules with enhanced bioactivity. One such molecule, belatacept, which inhibits the T-cell costimulatory pathway, has been shown to improve long-tern transplant outcome as part of a calcineurin inhibitor-free maintenance imnmunosuppressive regimen. The specialized immunosuppressive agents currently in clinical use, in preclinical development, and in early clinical trials for transplantation are discussed in this review.