Methods of Inducing Immune Tolerance Using Immunotoxins

Methods of Inducing Immune Tolerance Using Immunotoxins

The invention concerns immunotoxins and methods of using the immunotoxins for the treatment of rejection response in a patient, including graft-versus-host disease and transplantation of organs, tissues and cells into a host. In a specific embodiment of the invention, the transplant involves pancreatic islet cells. The immunotoxins are targeted via an antibody that is specific to T cells. This allows the specific ablation of resting T cells, resulting in an accentuation of immune tolerizing responses and an increased tolerance to transplants and grafts. The toxin portion of the immunotoxin is genetically engineered to maintain bioactivity when recombinantly produced in Pichia pastoris. Data are available in transgenic animals expressing human CD3epsilon which supports the effects of the immunotoxin against T cells.
Abstract: 
The invention concerns immunotoxins and methods of using the immunotoxins for the treatment of rejection response in a patient, including graft-versus-host disease and transplantation of organs, tissues and cells into a host. In a specific embodiment of the invention, the transplant involves pancreatic islet cells. The immunotoxins are targeted via an antibody that is specific to T cells. This allows the specific ablation of resting T cells, resulting in an accentuation of immune tolerizing responses and an increased tolerance to transplants and grafts. The toxin portion of the immunotoxin is genetically engineered to maintain bioactivity when recombinantly produced inPichia pastoris. Data are available in transgenic animals expressing human CD3epsilon which supports the effects of the immunotoxin against T cells.
Benefits: 
Specificity of the immunotoxin avoids the killing of other cells, reducing side-effects associated with other mechanisms of treatment (X-ray and cyclophosphamide) such as infection and induced malignancy. - A GMP production process for the immunotoxin has already been successfully implemented.
applications: 
Inventors: 

David Neville Jr (NIMH)

Patent Number: 
09/573,797 US Application No. 13/443,779 US Applic
Internal Laboratory Ref #: 
E-012-1991/0 Updated: Nov 9, 2015
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