The UCLA Delayed Immunological Tolerance after Kidney Transplantation Program
Grant Award Details
Grant Type:
Grant Number:
CLIN2-14796
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Cell Line Generation:
Award Value:
$6,717,608
Status:
Pre-Active
Grant Application Details
Application Title:
The UCLA Delayed Immunological Tolerance after Kidney Transplantation Program
Public Abstract:
Therapeutic Candidate or Device
CD34+ hematopoietic stem/progenitor cells (HSPC) and CD3+ cells
Indication
Phase I/II trial evaluating the safety/efficacy of infusion of donor CD34+ HSPCs and CD3+ T cells into recipients with HLA-identical kidney allograft.
Therapeutic Mechanism
Subjects who meet criteria will be taken off tacrolimus in Month 12 and followed for 48 months after HPSC infusion. They will be monitored for chimerism, graft rejection, GVHD, kidney function, and complications such as infection, malignancy, hypertension, diabetes, and cardiovascular disease. The results of this study will be critical in future trials that aim at removing immunosuppressive therapy from the patient’s daily regimen and improve the lifespan of the transplanted kidney.
Unmet Medical Need
The standard of care post-transplant remains triple-therapy immunosuppression, which predisposes patients to short- and long-term complications, including nephrotoxicity and re-transplantation. This study can free patients from immunosuppression and prolong the lifespan of the patient and allograft.
Project Objective
Maintain stable graft function without drugs.
Major Proposed Activities
CD34+ hematopoietic stem/progenitor cells (HSPC) and CD3+ cells
Indication
Phase I/II trial evaluating the safety/efficacy of infusion of donor CD34+ HSPCs and CD3+ T cells into recipients with HLA-identical kidney allograft.
Therapeutic Mechanism
Subjects who meet criteria will be taken off tacrolimus in Month 12 and followed for 48 months after HPSC infusion. They will be monitored for chimerism, graft rejection, GVHD, kidney function, and complications such as infection, malignancy, hypertension, diabetes, and cardiovascular disease. The results of this study will be critical in future trials that aim at removing immunosuppressive therapy from the patient’s daily regimen and improve the lifespan of the transplanted kidney.
Unmet Medical Need
The standard of care post-transplant remains triple-therapy immunosuppression, which predisposes patients to short- and long-term complications, including nephrotoxicity and re-transplantation. This study can free patients from immunosuppression and prolong the lifespan of the patient and allograft.
Project Objective
Maintain stable graft function without drugs.
Major Proposed Activities
- This project will enroll 10 recipients and 10 donors over the course of the study. Patients will be followed for a total of 48 months.
- The project will manufacture CD34+ HSPC and CD3+ cells for the recipient infusions according to the manufacturing plan outlined in the protocol.
- The project will evaluate immune monitoring assays as risk assessment tools and test how mixed chimerism impacts donor and recipient immune cells.
Statement of Benefit to California:
The waiting time in the US is over 5 years, with California hard hit with much longer average waiting times compared to residents in other parts of the US. By avoiding allograft loss through tolerance this would reduce the need for re-transplantation, helping both the patient and other transplant candidates who are in need of a kidney and would have less competition, resulting in improved transplantation rates, a component of the 2019 executive order on advancing American kidney health.
