• 1
    Vincenti F. What's in the pipeline? New immunosuppressive drugs in transplantation. Am J Transplant 2002; 2: 898903.
  • 2
    Vincenti F, Klintmalm G, Halloran PF. Open letter to the FDA: New drug trials must be relevant. Am JTransplant 2008; 8: 733734.
  • 3
    Meier-Kriescher HU, Schold JD, Srinivas TR, Kaplan B. Lack of improvement in renal allograft survival despite a marked decrease in acute rejection rates over the most recent era. Am J Transplant 2004; 4: 378383.
  • 4
    Aspeslet L, Freitag D, Trepanier D et al. ISA(TX)247: A novel calcineurin inhibitor. Transplant Proc 2001; 33: 10481051.
  • 5
    Stalder M, Birsan T, Hubble RW, Paniagua RT, Morris RE. In vivo evaluation of the novel calcineurin inhibitor ISATX247 in non-human primates. J Heart Lung Transplant 2003; 22: 13431352.
  • 6
    Gaber AO, Busque S, Mulgaonkar S, Gaston R, Jevnikar A, Meier-Kriesche H-U. ISA247: A phase IIB multicenter, open label, concentration-controlled trial in de novo renal transplantation. (abstract LB06) Am J Transplant 2008; 8(Suppl 2): 336.
  • 7
    Podder H, Kahan BD. Janus kinase 3: A novel target for selective transplant immunosuppression. Expert Opin Ther Targets 2004; 8: 613629.
  • 8
    Saemann MD, Zeyda M, Stulnig TM et al. Janus kinase-3 (JAK3) inhibition: A novel immunosuppressive option for allogeneic transplantation. Transpl Int 2004; 17: 481489.
  • 9
    Changelian PS, Flanagan ME, Ball DJ et al. Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor. Science 2003; 302: 875878.
  • 10
    Borie DC, Changelian PS, Larson MJ et al. Immunosuppression by the JAK3 inhibitor CP-690,550 delays rejection and significantly prolongs kidney allograft survival in nonhuman primates. Transplantation 2005; 79: 791801.
  • 11
    Busque S, Leventhal J, Brennan D et al. CP-690,550, a JAK3 inhibitor, in de novo kidney transplant recipients: 6-month results of a phase 2 trial (abstract). Am J Transplant 2007; 7(Suppl 2): 304.
  • 12
    Tan SL, Parker PJ. Emerging and diverse roles of protein kinase C in immune cell signaling. Biochem J 2003; 376: 545552.
  • 13
    Evenou J-P, Brinkmann V, Towbin H et al. Enzymatic and cellular characterization of NVP-AEB071 (AEB), a novel and selective protein kinase C (PKC) inhibitor that blocks early T cell activation, and its use to define the role of PKC in T cells (abstract). Am J Transplant 2006; 7(Suppl 2): 1026.
  • 14
    Evenou J-P, Thuille N, Cottens S et al. NVP-AEB071 (AEB), a novel protein kinase C inhibitor, abrogates early mouse T cell activation without affecting activation induced cell death (abstract). Am J Transplant 2006; 6(Suppl 2): 1029.
  • 15
    Bruns C, Pally C, Beerli C et al. NVP-AEB071 (AEB), a novel oral inhibitor of early T-cell activation, prolongs rat cardiac allograft survival when used alone and in combination with cyclosporine, Everolimus or FTY720 (abstract). Am J Transplant 2006; 6: 316.
  • 16
    Wagner J, Evenou J-P, Zenke G et al. The first-in-class oral protein kinase C (PKC) inhibitor NVP-AEB071 (AEB) prolongs renal allograft survival in non-human primates and suppresses lymphocyte proliferation at safe exposures in human proof-of-concent studies (abstract). Am J Transplant 2006; 6(Suppl 2): 86.
  • 17
    Bigaud M, Wieczorek G, Riesen S et al. NVP-AEB071 (AEB), a novel oral inhibitor of early T-cell activation, prolongs the survival of non-human primate kidney allografts when used a monotherapy or at non-effective doses combined with a non-effective dose of cyclosporine (abstract). Am J Transplant 2006; 6(Suppl 2): 250.
  • 18
    Bigaud M, Wieczorek G, Preussing E et al. NVP-AEB071 (AEB), the novel oral inhibitor of protein kinase C and early T-cell activation, prolongs non-human primates kidney allograft survival when combined with Everolimus, ERL080 or FTY720 without calcineurin inhibitor (abstract). Am J Transplant 2006; 6(Suppl 2): 251.
  • 19
    Slade A, Jung T, Hijazi Y et al. AEB071: Safety and activity of a novel T-cell activation inhibitor in psoriasis patients (abstract 1725). Presented at the 2007 American Transplant Congress; May 5–9, 2007; San Francisco , CA, USA .
  • 20
    Vincenti F. Chronic induction: What's new in the pipeline. In: RoncoC, ChiaramonteS, RemuzziG, eds. Kidney transplantation: Strategies to prevent organ rejection. Basel , Switzerland : Karger, 2005: 2229.
  • 21
    Reichert JM. Monoclonal antibodies in the clinic. Nat Biotechnol 2001; 19: 819822.
  • 22
    Larsen CP, Pearson TC, Adams AB et al. Rational development of LEA29Y (belatacept), a high-affinity variant of CTLA4-Ig with potent immunosuppressive properties. Am J Transplant 2005; 5: 443453.
  • 23
    Vincenti F, Mendez R, Pescovitz M. A phase I/II randomized open-label multicenter trial of efalizumab, a humanized anti-CD11a, anti-LFA-1 in renal transplantation. Am J Transplant 2007; 7: 17701777.
  • 24
    Da Silva AJ, Brickelmaier M, Majeau GR et al. Alefacept, an immunomodulatory recombinant LFA-3/IgG1 fusion protein, induces CD16 signaling and Cd2/Cd16-dependent apoptosis of CD2+ cells. J Immunology 2002; 168: 44624471.
  • 25
    Sayegh MH, Turka LA. The role of T-cell costimulatory activation pathways in transplant rejection. N Engl J Med 1998; 338: 18131821.
  • 26
    Vincenti F. Costimulation blockade in autoimmunity and transplantation. Journal Allergy Clinical Immunology 2008; 121: 299306.
  • 27
    Vincenti F, Larsen C, Durrbach A et al. Costimulation blockade with belatacept in renal transplantation. N Engl J Med 2005; 353: 770781.
  • 28
    Kirk AD, Burkly LC, Batty DS et al. Treatment with humanized monoclonal antibody against CD154 prevents acute renal allograft rejection in nonhuman primates. Nat Med 1999; 5: 686693.
  • 29
    Kirk AD, Knechtle SJ, Sollinger HW et al. Preliminary results of the use of humanized anti-CD154 in human renal allotransplantation (abstract). Am J Transplant 2001; 1(Suppl 1): 191.
  • 30
    Aoyagi T, Suzuki T, Sugitani A et al. A novel human anti-CD40 monoclonal antibody, 4D11, for kidney transplantation in cynomolgus monkeys, effect of induction and maintenance therapy (abstract #3). Amer J Transplant 7(Suppl 2): 147.
  • 31
    Suntharalingham G, Perry MR, Ward S et al. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Eng J Med 2006; 355: 10181028.
  • 32
    Shiao SL, McNiff JM, Masunaga T, Tamura K, Kubo K, Pober JS. Immunomodulatory properties of FK734, a humanized anti-CD28 monoclonal antibody with agonistic and antagonistic activities. Transplantation 2007; 83: 304313.
  • 33
    Nicolls MR, Gill RG. LFA-1 (CD11a) as a therapeutic target. Am J Transplant 2006; 6: 2736.
  • 34
    Posselt A, Szot G, Frassetto L et al. Islet allograft survival in type 1 diabetics using a calcineurin-free protocol based on efalizumab and sirolimus (abstract #216). Am J Transplant 2008; 8(Suppl 2): 235.
  • 35
    Krueger GG. Clinical response to alefacept: Results of a phase 3 study of intravenous administration of alefacept in patients with chronic plaque psoriasis. European Acad Dermatol and Verereology 2003; 17(Suppl 2): 1724.
  • 36
    Weaver TA, Carafeddine AH, Agarwal A et al. Targeting of costimulation blockade resistant T effector memory (TEM) cells in non-human primate renal transplantation with LFA-3-Ig (Alefacept) prolongs allograft survival (abstract 94). 2008; 8(Suppl 2): 204.
  • 37
    Kaplon RJ, Hochman PS, MIchler RE et al. Short course single agent therapy with an LFA-3-IgG1 fusion protein prolongs primate cardiac allograft survival. Transplantation 1996; 61: 356363.
  • 38
    Dhanireddy KK, Bruno DA, Zhang X, Leopardi F, Johnson LB, Kirk A. Alefacept (LFA3-Ig), portal venous donor specific transfusion, and sirolimus prolong renal allograft survival in non-human primates (abstract #1627). Presented at World Transplant Congress July 24, 2006.
  • 39
    Amersi F, Farmer DG, Shaw GD et al. P-selectin glycoprotein ligand-1 (rPSGL-Ig)-mediated blockade of Cd62 selectin molecules protects rat steatotic liver grafts from ischemia/reperfusion injury. Amer J Transplant 2002; 2: 600608.
  • 40
    Brown KM, Kondeatis E, Vaughan RW et al. Influence of donor C3 allotype on late renal-transplantation outcome. N Engl J Med 2006; 354: 20142023.
  • 41
    Wang H, Arp J, Liu W et al. Inhibition of terminal complement components in presensitized transplant recipients prevents antibody-mediated rejection leading to long-term graft survival and accommodation. J Immunol. 2007; 179: 44514463.
  • 42
    Li JS, Jaggers J, Anderson PA. The use of TP10, soluble complement receptor 1, in cardiopulmonary bypass. Expert Rev Cardiovascular Ther 2006; 4: 649654.
  • 43
    Pescovitz MD. Rituximab, an anti-CD20 monoclonal antibody: History and mechanism of action. Am J Transplant 2006; 6: 859866.
  • 44
    Woodland RT, Schmidt MR, Thompson CB. BLyS and B cell homeostasis. Semin Immunol 2006; 18: 318326.
  • 45
    Schneider P. The role of APRIL and BAFF in lymphocyte activation. Curr Opin Immunol 2005; 17: 282289.
  • 46
    Dillon SR, Gross JA, Ansell SM, Novak AJ. An APRIL to remember: Novel TNF ligands and therapeutic agents. Nat Rev Drug Discov 2006; 5: 235246.
  • 47
    Vugmeyster Y, Seshasayee D, Chang W et al. A soluble BAFF antagonist, BR3-Fc, decreases peripheral blood B cells and lymphoid tissue marginal zone and follicular B cells in cynomolgus monkeys. Am J Pathol 2006; 168: 476489.
  • 48
    Hideshima T, Mitsiades C, Akiyama M et al. Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341. Blood 101: 15301534.
  • 49
    Nishimoto N, Yoshizaki K, Maeda K et al. Toxicity, pharmacokinetics, and dose-finding study of repetitive treatment with the humanized anti-interleukin 6 receptor antibody MRA in rheumatoid arthritis. Phase I/II clinical study. J Rheumatol 2003; 30: 14261435.
  • 50
    Jones SA, Horiuchi S, Topley N, Yamamoto N, Fuller GM. The soluble interleukin 6 receptor: Mechanisms of production and implications in disease. FASEB Journal 2001; 15: 43.
  • 51
    Weaver TA, Charfeddine AH, Leopardi FV et al. Pre-clinical assessment of Genz-29155, a novel small molecule inhibitor of apoptosis with anti-rejection effects in non-human primates [Abstract #192]. Amer J Transplant 2008; 8(Suppl 2): 229.