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

NCT04661254 | Unknown

• 2 other identifiers: APHP2007332020-A01871-38
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 2

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.

Conditions

Kidney Transplantation; Liver Transplantation

Outcome Measures

Primary Outcomes (1)

• Validate 4 preclinical batches of Treg cells from 2 liver transplant patients and 2 kidney transplant patients

  Treg cells produced according to the expansion protocol defined by verifying the compliance of the batches according to the requirements of the guidelines on Good Manufacturing Practice specific to Advanced Therapy Medicinal Product) by respecting the validation and batch release criteria defined in this protocol.

  At day 10

Study Arms (1)

Lymphapheresis

OTHER

Blood is drawn from one of the patient's two arms and passes through a separation circuit. After removing the white blood cells, it is reinjected into the other arm.

Other: Lymphapheresis

Interventions

Lymphapheresis OTHER

\- 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

Lymphapheresis

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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;

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (2)

Pitié Salpêtrière hospital

Paris, 75013, France

Location

Pitié Salpêtrière hospital

Paris, 75013, France

Location

MeSH Terms

Interventions

Leukapheresis

Intervention Hierarchy (Ancestors)

Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques

Study Officials

• MIYARA Makoto, MD, PhD

  AP-HP - Pitié Salpêtrière hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

MIYARA Makoto, MD, PhD

CONTACT

+33 1 42 17 84 91; makoto.miyara@aphp.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2020
• First Posted: December 10, 2020
• Study Start: April 15, 2023
• Primary Completion: April 30, 2024
• Study Completion: April 30, 2024
• Last Updated: March 28, 2023

Record last verified: 2023-03

Locations

FR (2)