B cell-targeted immunotherapy for type 1 diabetes: What can make it work?
Immunotherapy has revolutionized treatment of cancers and autoimmune diseases. Bucking the trend, however, is type 1 diabetes (T1D), although it is one of best understood autoimmune diseases and individuals at genetic risk are identifiable with high certainty. Here we review the major obstacles associated with pan-B-cell-depletion using rituximab (RTX) and discuss the notion that B cell-directed therapy may be most effective as a preventive measure. We suggest that it will be more productive to aim at identifying and targeting autoreactive B cells rather than making adjustments to pan-B cell depletion and that non-conventional alternative therapies such as antibody blockade of FasL to bolster IL-10-producing Breg cells, which work successfully in mice, should be considered.
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Abdel Rahim A
AR
Hamad
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Rizwan
R
Ahmed
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Thomas
T
Donner
Diabetes Research Institute (DRI), IRCCS San Raffaele Scientific Institute, Milan, Italy.
Georgia
G
Fousteri
D000818:Animals; D018951:Antigens, CD20 / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002986:Clinical Trials as Topic; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D004359:Drug Therapy, Combination; D053222:Fas Ligand Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D016753:Interleukin-10 / Q000378:metabolism; D007515:Islets of Langerhans / Q000276:immunology; D016381:Islets of Langerhans Transplantation / Q000276:immunology; D051379:Mice; D000069283:Rituximab / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D018951:Antigens, CD20; D053222:Fas Ligand Protein; D007155:Immunologic Factors; D016753:Interleukin-10; D000069283:Rituximab