Columbia University

Technology Ventures

Specific T suppressor cells for the suppression of immune rejection

Technology #1587

The tolerance to self and other innocuous antigens is essential to a well-functioning immune system. This is also true for tolerance of allograft and xenograft organ and tissue transplants. Both autoimmune disease and transplant rejection result in severe tissue damage and remain largely unpredictable. The ability to diagnose and predict a mistargeted immune response, as well as to counteract it would be priceless, especially considering the dearth of organ donors and the toxicity and non-specificity of current immunosuppressive drugs. This technology provides a method of harnessing the body’s own immune machinery to trigger the acceptance of foreign tissue in transplant patients without the need for toxic and nonspecific immunosuppressant drugs.

Targeted T suppressor cells increase immune tolerance of foreign grafts, increasing the chances of success in transplant operations without the need for immunosuppressants

The invention includes methods for detecting and treating tissue, organ and cell transplant rejection as well as a method for the treatment of autoimmune flare ups. By harnessing a specialized subset of T suppressor (Ts) cells expressing a specific combination of genes (CD8+ CD28- FoxP3+ BCL6high DUSP10high, SOCS1high,miR-21low,miR-30blow, miR-155low) this technology can both detect and suppress immune responses. These specialized Ts cells interact directly with antigen-presenting cells (APCs) such as dendritic cells and monocytes as well as endothelial cells (ECs). The interaction of the Ts cells with APCs and ECs increases the expression of the immune inhibitory receptors ILT3 and ILT4 in the APCs and ECs, and these transcriptional changes render them tolerant of foreign tissue in an antigen-specific manner. This technology uses a soluble ILT3-Fc fusion protein to induce the generation of CD8+ CD28- FoxP3+ Ts cells, which can then suppress immune rejection in a patient after transplantation. Furthermore, CD8+ CD28- FoxP3+ Ts cells specific for the donor tissue can be detected in the transplant recipient’s blood and used to predict the potential and severity of an immune rejection event. Because this technology makes use of the patient’s own immune system, it can achieve extremely high specificity, tuning the immune system to tolerate only the specified foreign tissue while functioning normally against foreign pathogens. Use of this technology would provide a vast improvement over current immunosuppressant therapies, which are costly, potentially toxic, and nonspecific, leaving patients susceptible to a large number of pathogens that a healthy immune system would readily combat.

Lead Inventor:

Nicole Suciu-Foca, Ph.D.

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

Patent information:

Patent Issued (US 8,207,110)

Tech Ventures Reference: IR 1587

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