SUPPRESSION OF TRANSPLANT REJECTION - Isis Project No 1439 & 2848

New method for generating regulatory T cell (Tregs) that avoids the need for cell sorting

Marketing Opportunity

Transplantation is the treatment of choice for end stage kidney, heart, liver and pancreas organ failure.  Despite considerable advances in the management of transplant rejection in recent years most transplants are still eventually rejected.  In addition, current immunosuppressive approaches leave transplant recipients more susceptible to infections and cancer.

The Oxford Invention

Researchers have devised two new methods for producing important regulatory T cells, known as Tregs. Tregs can control destructive rejection responses so that donor organs are less likely to be rejected by a recipient’s immune system.  Other methods for ex vivo Treg generation are known but their use is limited by the requirement for cell sorting using flow cytometry.

The patent applications describe novel methods for the generation of Tregs both in vivo and ex vivo.

• For in vivo generation, immunisation with a non-cellular antigen combined with a monoclonal antibody to CD4 T cells is followed by a second challenge with the non-cellular antigen at or near the point of transplantation. This approach can also be used ex vivo.

• For additional ex vivo generation, recipient CD4 T cells are cultured with TGF-b conditioned donor type antigen presenting cells in the presence of IFN-g.  This leads to preferential death of effector cells, expansion of naturally occurring Treg and conversion of non-Treg precursors resulting in an enrichment for donor-reactive Treg.

In a clinical context, patients would be pre-exposed to the in vivo therapy before transplantation and their resulting Treg population maintained by re-challenging with the non-cellular antigen until transplantation.  This approach does not require that the identity of the organ donor is known before the therapy commences. The ex vivo approaches could enable the administration of regulatory T cells as a cellular therapy to control transplantation rejection at the time of transplantation, or at any point thereafter, to ensure that control of rejection is maintained.   The in vivo and ex vivo approaches have the potential to be used in combination. This approach is also potentially applicable for the treatment of autoimmunity.

Patent Status

The patent applications are available for licence and we are actively seeking partners for the licensing and commercial development of this technology.

Request Further Information: Project Number 1439& 2848 Suppression of Transplant Rejection