NCT04661254

Treg Cell Therapy in Liver and Kidney Transplantation - Preclinical Validation of Batches of Treg Cells Amplified in Vitro

• Status: Unknown
• Phase: N/A
• Study type: Interventional
• Enrollment: 4 (estimated)
• Sponsor: Assistance Publique - Hôpitaux de Paris · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

Kidney and liver transplantation requires a fine tuning of immune responses in order to achieve long term operational tolerance with immunosuppressants or immune modulators. Numerous experimental findings indicate that CD4+ FOXP3 expressing regulatory T (Treg) cells play a central role in the induction of tolerance to the grafts indicating that the use of Treg cells may be an innovative therapeutic strategy in kidney transplantation that would enable the diminution of immunosuppressive drugs or even their discontinuation, thus decreasing their risk of adverse events. As human Treg cells represent less than 10% of CD4+ T cells, and because it has been shown in mice that a dose of 2\*104 polyclonal Tregs/g was necessary to induce tolerance in animal models of solid organ transplantation, it is mandatory to expand human Treg cells ex vivo, after isolating them from peripheral blood. The investigators previously defined a protocol for Treg cell isolation and expansion in clinical grade conditions (cGMP) that enabled us to obtain the expected number of expanded cells maintaining high levels of FOXP3 (3). The investigators therefore hypothesize in humans, as it has been already shown in mice, that the infusion of autologous expanded polyclonal Treg cells would lead to the obtaining of operational tolerance in kidney and liver graft in association with classical immunosuppressants and an expectable diminution of those. To this end, it is necessary to have pre-clinical batches of expanded Treg cells validated by the National Agency for Medicines and Health Products Safety validate (ANSM). The investigators therefore plan to have 4 batches from 2 liver transplant patients and 2 kidney transplant patients validated.

Conditions

• Kidney Transplantation
• Liver Transplantation

Interventions

Type	Name	Description
OTHER	Lymphapheresis	\- From the blood product of lymphapheresis: Autologous naïve regulatory CD45RA+CD4+CD25+FoxP3+ T lymphocytes (Tregs) selected and amplified ex vivo; obtained by selection and sorting of CD4+CD25 +CD127lowCD45RA+ cells, derived from lymphapheresis and amplified ex vivo for 10 +/- 1 days, under cGMP condition in the presence of IL2 and Rapamycin

Timeline

• Start date: 2023-04-15
• Primary completion: 2024-04-30
• Completion: 2024-04-30
• First posted: 2020-12-10
• Last updated: 2023-03-28

Locations

2 sites across 1 country: France