De novo belatacept in clinical vascularized composite allotransplantation

Most immunosuppressive regimens used in clinical vascularized composite allotransplantation (VCA) have been calcineurin inhibitor (CNI)‐based. As such, most recipients have experienced CNI‐related side effects. Costimulation blockade, specifically CD28/B7 inhibition with belatacept, has emerged as a clinical replacement for CNI‐based immunosuppression in kidney transplantation. We have previously shown that belatacept can be used as a centerpiece immunosuppressant for VCA in nonhuman primates, and subsequently reported successful conversion from a CNI‐based regimen to a belatacept‐based regimen after clinical hand transplantation. We now report on the case of a hand transplant recipient, whom we have successfully treated with a de novo belatacept‐based regimen, transitioned to a CNI–free regimen. This case demonstrates that belatacept can provide sufficient prophylaxis from rejection without chronic CNI‐associated side effects, a particularly important goal in nonlifesaving solid organ transplants such as VCA.

[1]  B. Pomahac,et al.  MMP3 Is a Non-invasive Biomarker of Rejection in Skin-Bearing Vascularized Composite Allotransplantation: A Multicenter Validation Study , 2019, Front. Immunol..

[2]  Jeffrey N. Browndyke,et al.  Neural activation for actual and imagined movement following unilateral hand transplantation: a case study , 2019, Neurocase.

[3]  A. Kirk,et al.  Belatacept Combined With Transient Calcineurin Inhibitor Therapy Prevents Rejection and Promotes Improved Long‐Term Renal Allograft Function , 2017, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[4]  A. Kirk,et al.  Tacrolimus to Belatacept Conversion Following Hand Transplantation: A Case Report , 2014, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[5]  A. Kirk,et al.  Studies Introducing Costimulation Blockade for Vascularized Composite Allografts in Nonhuman Primates , 2015, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[6]  E. Kulbokas,et al.  Transcriptional Profiling of Belatacept and Calcineurin Inhibitor Therapy in Renal Allograft Recipients , 2014, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[7]  A. Kirk,et al.  Renal Transplantation Using Belatacept Without Maintenance Steroids or Calcineurin Inhibitors , 2014, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[8]  L. Rostaing,et al.  Long‐Term Belatacept Exposure Maintains Efficacy and Safety at 5 Years: Results From the Long‐Term Extension of the BENEFIT Study , 2013, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[9]  A. Kirk,et al.  CD40‐Specific Costimulation Blockade Enhances Neonatal Porcine Islet Survival in Nonhuman Primates , 2011, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[10]  W. Marks,et al.  Immunosuppression with Belatacept‐Based, Corticosteroid‐Avoiding Regimens in De Novo Kidney Transplant Recipients , 2011, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[11]  G. Lucchini,et al.  INTERNATIONAL REGISTRY ON HAND AND COMPOSITE TISSUE TRANSPLANTATION. , 2006 .

[12]  Jean Kanitakis The challenge of dermatopathological diagnosis of composite tissue allograft rejection: a review , 2008, Journal of cutaneous pathology.

[13]  A. Kirk,et al.  The Banff 2007 Working Classification of Skin‐Containing Composite Tissue Allograft Pathology , 2008, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[14]  A. Kirk,et al.  Costimulation blockade: towards clinical application. , 2008, Frontiers in bioscience : a journal and virtual library.

[15]  A. Kirk,et al.  A New Look at Blockade of T‐cell Costimulation: A Therapeutic Strategy for Long‐term Maintenance Immunosuppression , 2006, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[16]  P. Linsley,et al.  Rational Development of LEA29Y (belatacept), a High‐Affinity Variant of CTLA4‐Ig with Potent Immunosuppressive Properties , 2005, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[17]  D. Harlan,et al.  Studies Investigating Pretransplant Donor-Specific Blood Transfusion, Rapamycin, and the CD154-Specific Antibody IDEC-131 in a Nonhuman Primate Model of Skin Allotransplantation1 , 2003, The Journal of Immunology.

[18]  D. Harlan,et al.  INDUCTION THERAPY WITH MONOCLONAL ANTIBODIES SPECIFIC FOR CD80 AND CD86 DELAYS THE ONSET OF ACUTE RENAL ALLOGRAFT REJECTION IN NON-HUMAN PRIMATES1 , 2001, Transplantation.

[19]  D. Harlan,et al.  Treatment with humanized monoclonal antibody against CD154 prevents acute renal allograft rejection in nonhuman primates , 1999, Nature Medicine.

[20]  A. Kirk Transplantation tolerance: a look at the nonhuman primate literature in the light of modern tolerance theories. , 1999, Critical reviews in immunology.

[21]  D. Harlan,et al.  CTLA4-Ig and anti-CD40 ligand prevent renal allograft rejection in primates. , 1997, Proceedings of the National Academy of Sciences of the United States of America.