Belatacept/CTLA4Ig: an update and critical appraisal of preclinical and clinical results

Expert Rev Clin Immunol. 2018 Jul;14(7):583-592. doi: 10.1080/1744666X.2018.1485489. Epub 2018 Jun 25.

Abstract

The B7/CD28/CTLA4 signaling cascade is the most thoroughly studied costimulatory pathway and blockade with CTLA4Ig (abatacept) or its derivative belatacept has emerged as a valuable option for pharmacologic immune modulation. Several clinical studies have ultimately led to the approval of belatacept for immunosuppression in kidney transplant recipients. Areas covered: This review will discuss the immunological background of costimulation blockade and recent preclinical data and clinical results of CTLA4Ig/belatacept. Expert commentary: The development of belatacept is a major advance in clinical transplantation. However, in spite of promising results in preclinical and clinical trials, clinical use remains limited at present, in part due to increased rates of acute rejection. Recent efforts showing encouraging progress in refining such protocols might be a step toward harnessing the full potential of costimulation blockade-based immunosuppression.

Keywords: CTLA4Ig; Costimulation blockade; transplantation.

Publication types

  • Review

MeSH terms

  • Abatacept / therapeutic use*
  • Animals
  • B7 Antigens / metabolism
  • CD28 Antigens / metabolism
  • CTLA-4 Antigen / metabolism
  • Clinical Trials as Topic
  • Drug Evaluation, Preclinical
  • Graft Rejection / drug therapy*
  • Humans
  • Immunosuppression Therapy
  • Kidney Transplantation*
  • Signal Transduction

Substances

  • B7 Antigens
  • CD28 Antigens
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Abatacept