Anti-CTLA-4 therapy may have mechanisms similar to those occurring in inherited human CTLA4 haploinsufficiency.

Abstract

The inhibitory anti-CTLA-4 antibody, ipilimumab, dramatically improved survival in a subgroup of metastatic melanoma patients. The majority, however, suffered autoimmune-related adverse events (irAEs), sometimes pathognomonic of acute graft-versus-host-disease (GVHD). This implies that the CTLA-4 blockade is not tumor specific. We make a risky but testable prediction: anti-CTLA-4 therapy may have mechanism similar to that occurring in inherited human CTLA-4 haploinsufficiency. If so, a therapeutic paradigm shift is required. The task is not desperately trying to put the genie back in the bottle by immune-suppressive treatments, but harnessing the immense forces liberated by the anti-CTLA-4 antibody blockade by pretargeting or dose adjustment.

• Authors: Tibor Bakacs, Jitendra N Mehrishi
• Journal: Immunobiology (Immunobiology) Vol. 220 Issue 5 Pg. 624-5 (May 2015) ISSN: 1878-3279 [Electronic] Netherlands
• PMID: 25638260 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 Elsevier GmbH. All rights reserved.

Chemical References

• Antibodies, Blocking
• Antibodies, Monoclonal
• CTLA-4 Antigen
• CTLA4 protein, human
• Ipilimumab

Topics

• Animals
• Antibodies, Blocking (adverse effects, therapeutic use)
• Antibodies, Monoclonal (adverse effects, therapeutic use)
• Autoimmune Diseases (etiology, prevention & control)
• CTLA-4 Antigen (antagonists & inhibitors, genetics)
• Clinical Protocols
• Haploinsufficiency (immunology)
• Homeostasis
• Humans
• Immunotherapy (adverse effects, methods)
• Ipilimumab
• Melanoma (complications, drug therapy, immunology)
• Mice
• Mice, Knockout
• Neoplasm Metastasis
• Skin Neoplasms (complications, drug therapy, immunology)