Clinical trial NCT04661254: Treg Cell Therapy in Liver and Kidney Transplantation - Preclinical Validation of Batches of Treg Cells Amplified in Vitro
Official title: Treg Cell Therapy in Liver and Kidney Transplantation - Preclinical Validation of Batches of Treg Cells Amplified in Vitro
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Kidney Transplantation
Liver Transplantation
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2020-12-10
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief 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.


Eligibility criteria: Inclusion Criteria:

For liver transplant patients:

* Liver transplantation carried out for 1 to 3 months for alcoholic cirrhosis;
* Normal liver biological test;
* Normal hepatic morphological assessment;

For kidney transplant patients:

* Renal transplantation carried out for 3 to 6 months for any disease requiring renal transplantation;
* Normal renal biological assessment;
* Normal renal morphological assessment;
* DSA \<1500 MFI at inclusion

Common criteria:

* Age ≥ 18 years and ≤ 70 years
* GB ≥1500 / mm3
* Hemoglobin level\> 10g / 100ml
* Platelets\> 50,000 / μl
* Weight\> 40Kg
* Informed and signed consent;
* Patient affiliated to a social security scheme

Exclusion Criteria:

For liver transplant patients:

- Hepatocellular carcinoma or history of another cancer;

For kidney transplant patients:

- Kidney cancer or a history of another cancer

Common criteria:

* Active infectious diseases: positive serology for hepatitis A, B or C, HIV, HTLV, CMV and EBV;
* Associated autoimmune disease, including type 1 diabetes;
* GB \<1500 / mm3;
* Any contraindication to citrate and calcium gluconate.
* Pregnancy or lactating woman
* Patient under guardianship or curatorship
* Patient deprived of liberty or under administrative security measure

Primary outcomes:
measure: Validate 4 preclinical batches of Treg cells from 2 liver transplant patients and 2 kidney transplant patients
timeFrame: At day 10
Secondary outcomes:
Other outcomes:
Locations:
city: Paris
country: France
facility: Pitié Salpêtrière hospital
city: Paris
country: France
facility: Pitié Salpêtrière hospital
Study officials:
affiliation: AP-HP - Pitié Salpêtrière hospital
name: MIYARA Makoto, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: