Columbia University

Technology Ventures

Transplant rejection therapy and autoimmune disease test and treatment

Technology #1672

“Name of the inventor: Nicole Suciu-Foca Diagnostic test for transplant tolerance, treatment of transplant rejection, and autoimmune disease test and treatment The invention includes methods for detecting and treating allograft transplant rejection, as well as for modulating the T cell immune response. A specialized subset of T suppressor (Ts) cells with the phenotype CD8+ CD28- FoxP3+ inhibits the activation of CD4+ T helper (Th) cells in an antigen-specific manner. It does so by interacting directly with specific antigen-presenting cells (APCs) such as dendritic cells and monocytes, as well as with endothelial cells (ECs), then inducing the upregulation of the inhibitory receptors ILT3 and ILT4 and the downregulation of costimulatory molecules. These transcriptional changes render the APCs and ECs tolerogenic (i.e., incapable of activating cognate CD4+ Th cells). The detection in the allograft recipient’s blood of CD8+ CD28- FoxP3+ Ts cells specific for the donor predicts future transplant tolerance. Similarly, soluble ILT3-Fc fusion protein, which induces the generation of CD8+ CD28- FoxP3+ Ts cells, is capable of treating transplant rejection in an antigen-specific manner. In fact, the manipulation of ILT3/ILT4 and their receptors has the potential to increase or decrease immunosupression in a variety of disorders.

Applications: • Diagnostic test for transplant tolerance • Treatment of transplant rejection with soluble ILT3-Fc fusion protein • Diagnostic test for autoimmune disease susceptibility • Treatment of autoimmune disease with soluble ILT3-Fc fusion protein • Reduction of immunosuppression in cases of AIDS, cancer by blocking ILT3/4 binding to receptors

Advantages • Novel cell phenotype suppresses the immune response in an antigen specific manner • Reduces the need for non-specific immunosuppressive drugs after organ transplant which make the patient susceptible to opportunistic infections • Peripheral blood lymphocytes diagnosable, obviating the need for biopsy • Applicable to many immune system dysfunctions ”