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Th188 - Transfer of CD8+ T Regulatory Cells GMP Manufacturing for Clinical Trial in Kidney Transplanted Patients

Thursday, June 22, 2023

7:30 AM – 7:30 PM

Sonia Salle – Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000, Nantes, France; Mariane Lucazeau – Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000, Nantes, France; Soraya Saiagh – UTCG, CHU Nantes, Nantes, France; Marie-Christine Pandolfino Lévêque – UTCG, CHU Nantes, Nantes, France; Cécile Braudeau – CHU Nantes, Nantes Université, Laboratoire d'Immunologie, CIMNA, Nantes, France; Mina Benjelloun Zahar – UTCG, CHU Nantes, Nantes, France; Florence Vrignaud – UTCG, CHU Nantes, Nantes, France; Béatrice Clémenceau – UTCG, CHU Nantes, Nantes, France; Régis Josien – Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000, Nantes, France; Maëlle Ningre – Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000, Nantes, France; Emmanuelle Papuchon – Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000, Nantes, France; Diego Cantarovich – Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000, Nantes, France; Ignacio Anegon – Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000, Nantes, France; Carole Guillonneau – Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000, Nantes, France

SB

Séverine Bézie, n/a

PhD
Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France
Nantes Cedex 1, Pays de la Loire, France
SS

Sonia Salle

Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000, Nantes, France
ML

Mariane Lucazeau

Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000, Nantes, France
SS

Soraya Saiagh

UTCG, CHU Nantes, Nantes, France
MP

Marie-Christine Pandolfino Lévêque

UTCG, CHU Nantes, Nantes, France
CB

Cécile Braudeau

CHU Nantes, Nantes Université, Laboratoire d'Immunologie, CIMNA, Nantes, France
MB

Mina Benjelloun Zahar

UTCG, CHU Nantes, Nantes, France
FV

Florence Vrignaud

UTCG, CHU Nantes, Nantes, France
BC

Béatrice Clémenceau

UTCG, CHU Nantes, Nantes, France
RJ

Régis Josien

Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000, Nantes, France
MN

Maëlle Ningre

Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000, Nantes, France
EP

Emmanuelle Papuchon

Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000, Nantes, France
DC

Diego Cantarovich

Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000, Nantes, France
IA

Ignacio Anegon

Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000, Nantes, France
CG

Carole Guillonneau

Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000, Nantes, France
SS

Sonia Salle

Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000, Nantes, France
ML

Mariane Lucazeau

Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000, Nantes, France
SS

Soraya Saiagh

UTCG, CHU Nantes, Nantes, France
MP

Marie-Christine Pandolfino Lévêque

UTCG, CHU Nantes, Nantes, France
CB

Cécile Braudeau

CHU Nantes, Nantes Université, Laboratoire d'Immunologie, CIMNA, Nantes, France
MB

Mina Benjelloun Zahar

UTCG, CHU Nantes, Nantes, France
FV

Florence Vrignaud

UTCG, CHU Nantes, Nantes, France
BC

Béatrice Clémenceau

UTCG, CHU Nantes, Nantes, France
RJ

Régis Josien

Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000, Nantes, France
MN

Maëlle Ningre

Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000, Nantes, France
EP

Emmanuelle Papuchon

Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000, Nantes, France
DC

Diego Cantarovich

Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000, Nantes, France
IA

Ignacio Anegon

Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000, Nantes, France
CG

Carole Guillonneau

Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000, Nantes, France

Abstract Text: CD8+ Treg cell therapy is effective in preclinical models but has never been evaluated in a clinical trial. We designed a phase 1/2a clinical trial of cell therapy using GMP manufactured autologous polyclonal CD8+ Tregs to treat kidney transplanted patients from living donors.
First, we set up a method for the isolation of CD8+Tregs from peripheral blood of healthy individuals using positive magnetic selection and flow cytometry in a safe closed system. We determined optimal clinical-grade culture conditions to preserve high proliferation rate, baseline phenotypic profile, and suppressive function in vitro and in vivo in a model of acute GVHD in NSG mice. We verified that they were resistant to classic maintenance immunosuppressive drugs, persistent and efficient in vivo but not cytotoxic. The method was validated on cells from patients with renal insufficiency, then transferred in the GMP facility with 3 validation runs demonstrating the phenotypic and functional stability of CD8+ Treg, meeting quality controls and release criteria.
The study will be a first-in-human, one-arm, open-label, prospective trial in patients with end-stage chronic renal failure requiring primary kidney transplantation, with 3 escalating doses of CD8+Tregs administered the day before the transplant without induction treatment and associated with classic maintenance immunosuppression. Patients will be monitored for long-term safety, immunosuppression burden and occurrences of infections. Transcriptomic and proteomic analyses on blood, biopsy, and urine samples will inform on persistence and migration of Tregs to the graft.