Anti-CD28 Antibody-Initiated Cytokine Storm in Canines

In the late 1990s, cytotoxic T-lymphocyte antigen 4-Ig was evaluated as an immune-modulating agent in the canine hematopoietic cell transplantation (HCT) model.1,2 CTLA4-Ig binds to B7.1 and B7.2 (CD80, CD86) expressed on antigen-presenting cells and prevents activation of both CD28 (costimulation) and CTLA-4 (coinhibition) expressed on either naive or activated T cells, respectively. When used in conjunction with the immunosuppressive agents, mycophenolate mofetil/cyclosporine or methotrexate/cyclosporine, CTLA4-Ig improved both donor hematopoietic cell engraftment and prevention of graft-versus-host disease (GVHD).1,2 Most recently, after additional data in nonhuman primates,3 the Pediatric Blood and Marrow Transplant Consortium developed a phase 2 clinical trial that uses CTLA4-Ig in combination with methotrexate/cyclosporine for GVHD prevention.