Transplantation of genetically modified haematopoietic stem cells to induce antigen-specific tolerance as a cure for autoimmune diseases.
Autoimmune diseases are incurable and are managed using therapeutic agents. Bone marrow transplantation is being trialled as a treatment for these diseases. While allogeneic bone marrow transplantation shows impressive benefit, its application is hindered by GVHD and high mortality. On the other hand, autologous bone marrow transplantation has lower mortality rate and no GVHD but is associated with higher relapse rates. Given that autoimmune diseases are a result of a failure of immune tolerance and that bone marrow-derived dendritic cells play an important role in establishing immune tolerance, the transplantation of genetically modified haematopoietic stem cells to generate molecular chimerism to induce antigen-specific tolerance offers the potential for developing a cure for autoimmune diseases. In this review, we will discuss key findings from clinical data and animal studies to provide evidence to support the above concept.
Chan
James
J
Centre for Inflammatory Diseases, Department of Medicine, Southern Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia. james.chan@med.monash.edu.au
Alderuccio
Frank
F
Toh
Ban-Hock
BH
D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D005818:Genetic Engineering; D015316:Genetic Therapy; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007165:Immunosuppression Therapy; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012038:Regeneration; D014182:Transplantation, Autologous
D001324:Autoantigens; D011993:Recombinant Fusion Proteins