(provided by the applicant) Current immune therapies are broad acting and commonly cause adverse drug reactions and long-term immune compromise, often culminating in infection, cancer and premature death. TOL101 targets a unique T-cell receptor protein (alpha beta-TCR) with the capacity to down regulate disease-causing T-cells in a manner that induces T-cell non-responsiveness, that is, operational tolerance. Induction of operational tolerance will potentially free patients from chronic administration of expensive and often toxic immune suppressing drugs.
The specific aim of this project is to determine the safety and preliminary efficacy of TOL101 in patients undergoing their first kidney transplantation. In this trial, standard safety evaluations will be performed. In addition, physicians will closely monitor for symptoms associated with cytokine release syndrome. Testing for specific infectious agents commonly observed in transplant patients will be conducted, while patients are monitored for other infections and malignancies. Secondary to these safety objectives, the pharmacokinetic profile as well as the effect of TOL101 on CD3+ lymphocytes and other leukocytes will be addressed. The ability to reduce and/or modulate alpha beta T cells, including those of memory phenotype, is critical to the prevention of allograft rejection. Furthermore, data suggest that agents that promote the expansion of regulatory T cells may also aid in the prevention of allograft loss due to transplant rejection. Using a central flow cytometry laboratory, the response of T cell subsets including regulatory T cells to TOL101 therapy will be examined. In addition, preliminary clinical efficacy information including renal function, biopsy results, graft and patient survival will be collected.

Public Health Relevance

Renal transplant patients continue to experience increased incidence of infections and malignancies, consequences of broad immune suppression to prevent rejection of their transplanted kidney. Together, these complications cost the healthcare system over $10 billion annually. TOL101 is expected to lower these costs by targeting the cause of rejection, allo-reactive T cells, while reducing the indirect costs associated with complications.

Agency
National Institute of Health (NIH)
Institute
Food and Drug Administration (FDA)
Type
Research Project (R01)
Project #
1R01FD004110-01A1
Application #
8366321
Study Section
Special Emphasis Panel (ZFD1-OPD-N (S1))
Project Start
2012-09-14
Project End
2013-08-31
Budget Start
2012-09-14
Budget End
2013-08-31
Support Year
1
Fiscal Year
2012
Total Cost
Indirect Cost
Name
Tolera Therapeutics, Inc.
Department
Type
DUNS #
796699721
City
Cleveland
State
OH
Country
United States
Zip Code
44106