Name:
Institution:
Type:
PI
Grant Award Details
Sequential same donor αβdepleted-HSCT from an HLA-partially matched donor allowing immunosuppression free kidney transplant
Grant Type:
Grant Number:
CLIN2-14024
Project Objective:
- Objective of this study is to assess sequential T cell receptor/CD19+ B cell depleted hematopoietic stem cell transplant in pediatric and adolescent and young adults with SIOD, FSGS, Cystinosis and SLE patients allowing immunosuppression free kidney transplant from the same donor
Investigator:
Disease Focus:
Anemia
Blood Disorders
Bone Marrow Transplant and Viral Infection
Human Stem Cell Use:
Adult Stem Cell
Cell Line Generation:
Adult Stem Cell
Award Value:
$11,998,188
Status:
Active
Grant Application Details
Application Title:
- Sequential same donor αβdepleted-HSCT from an HLA-partially matched donor allowing immunosuppression free kidney transplant
Public Abstract:
Therapeutic Candidate or Device
Mobilized peripheral blood stem cells from allogeneic donors depleted of TCRαβ+ T cells/CD19+ B cells
Indication
Renal failure due to one of four genetic and/or immunological diseases
Therapeutic Mechanism
1. By using haploidentical parents, we will expand the number of potential living donors, and 2. with pre-HSCT immune ablation we can cure the underlying immune associated disease reducing the risk of disease recurrence in the newly engrafted kidney, and 3. with the establishment of a full donor lymphoid engraftment, we eliminate the risk of kidney rejection and the need of lifelong immunosuppression. Therefore, the likelihood of a second kidney transplant will be reduced, if not eliminated.
Unmet Medical Need
Our same donor sequential αβdepleted-HSCT kidney transplantation strategy addresses the urgent unmet medical need to abrogate the need for post-kidney transplant lifelong immunosuppression, the risk of chronic rejection, and, ultimately, the need for repeated transplantation.
Project Objective
Phase 1b trial completed
Major Proposed Activities
- Perform αβdepleted-HSCT and achieve complete donor engraftment without severe GvHD
- Perform post-αβdepleted-HSCT kidney transplantation and discontinuation of the immunesuppression within 90 days post-KT
- Develop a closed system for production of αβdepleted-HSC to expand the number of facilities able to provide αβdepleted-HSC manufacturing
Statement of Benefit to California:
California performs ~ 100 pediatric KT/year of which ~50 patients experience rejection. These patients enter a cycle of dialysis and waiting for a new kidney creating a quality of life and healthcare burden. Sequential same donor αβdepleted-HSCT/KT can 1) eliminate the need for lifelong immunosuppression, 2) reduce the need for a 2nd KT, and 3) cure the underlying disease, resulting in improved lives of patients, decreased societal costs and enormous socio-economic benefit to California.
