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Novel Immunosuppression: Small Molecules and Biologics

  • Julie M. Yabu
    Affiliations
    Department of Medicine, University of California, San Francisco, Kidney Transplant Service, San Francisco, CA.
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  • Flavio Vincenti
    Correspondence
    Address reprint requests to Flavio Vincenti, MD, University of California, San Francisco, Kidney Transplant Service, 505 Parnassus Ave, Room 884M, San Francisco, CA 94143-0780.
    Affiliations
    Department of Medicine, University of California, San Francisco, Kidney Transplant Service, San Francisco, CA.

    Department of Surgery, University of California, San Francisco, Kidney Transplant Service, San Francisco, CA.
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      Summary

      Kidney transplantation today has excellent short-term outcomes that have paralleled the use of new immunosuppressive agents introduced in the 1990s. In addition to reducing acute rejection, the goals for developing new agents is to improve long-term outcome, minimize nephrotoxicity, and reduce infectious, cardiovascular, and malignancy-related complications. Novel small molecules and biological agents currently in clinical development may help to minimize the use of calcineurin inhibitors and steroids. These small molecules include FTY720, a sphingosine phosphate–receptor modulator, FK778, an inhibitor of pyrimidine synthesis, CP-690550, a JAK3 inhibitor, and AEB-071, a protein kinase C inhibitor. The biological agents include drugs targeting interleukin-15, anti-CD40, belatacept (LEA29Y), a second-generation CTLY4Ig that blocks the interaction between CD80/86 and CD28 costimulatory pathways, and efalizumab, a humanized anti-LFA1 monoclonal antibody. These new agents currently in preclinical and clinical trials appear promising and may represent the emergence of novel immunosuppressive agents that can deliver immunosuppression without long-term toxicity.

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