Tu44 - Immunotherapy Using IL-34 for the Treatment of GvHD and Solid Organ Rejection: Strategies for its Optimisation

Tuesday, June 21, 2022

6:15 PM – 7:45 PM PT

Presenting Author(s)

AS

Apolline Salama, n/a

Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000 Nantes, France; LabEx IGO “Immunotherapy, Graft, Oncology”, Nantes, France
Nantes, Pays de la Loire, France

Co-Author(s)

AF

Antoine Freuchet, n/a

Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000 Nantes, France; LabEx IGO “Immunotherapy, Graft, Oncology”, Nantes, France
Nantes, Pays de la Loire, France
AQ

Agnès Quéméner, n/a

Université de Nantes, CNRS, Inserm, CRCINA, F-44000 Nantes, France; LabEx IGO “Immunotherapy, Graft, Oncology”, Nantes, France
Nantes, Pays de la Loire, France
NJ

Noémie Joalland, n/a

Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000 Nantes, France; LabEx IGO “Immunotherapy, Graft, Oncology”, Nantes, France
Nantes, Pays de la Loire, France
RH

Romain Humeau, n/a

Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000 Nantes, France; LabEx IGO “Immunotherapy, Graft, Oncology”, Nantes, France
Nantes, Pays de la Loire, France
MM

Mike Maillasson, n/a

Université de Nantes, CNRS, Inserm, CRCINA, F-44000 Nantes, France; LabEx IGO “Immunotherapy, Graft, Oncology”, Nantes, France; Université de Nantes, Inserm, CNRS, CHU Nantes, SFR Santé, FED 4203, Inserm UMS 016, CNRS, UMS 3556, IMPACT Platform, Nantes, France
Nantes, Pays de la Loire, France
SB

Séverine Bézie, n/a

Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000 Nantes, France; LabEx IGO “Immunotherapy, Graft, Oncology”, Nantes, France
Nantes, Pays de la Loire, France
NV

Nadège Vimond, n/a

Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, F-44000 Nantes, France; LabEx IGO “Immunotherapy, Graft, Oncology”, Nantes, France
Nantes, Pays de la Loire, France
IB

Isabelle Barbieux, n/a

Université de Nantes, CNRS, Inserm, CRCINA, F-44000 Nantes, France; LabEx IGO “Immunotherapy, Graft, Oncology”, Nantes, France
Nantes, Pays de la Loire, France
EM

Erwan Mortier, n/a

Université de Nantes, CNRS, Inserm, CRCINA, F-44000 Nantes, France; LabEx IGO “Immunotherapy, Graft, Oncology”, Nantes, France; Université de Nantes, Inserm, CNRS, CHU Nantes, SFR Santé, FED 4203, Inserm UMS 016, CNRS, UMS 3556, IMPACT Platform, Nantes, France
Nantes, Pays de la Loire, France
IA

Ignacio Anegon, n/a

Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France; LabEx IGO “Immunotherapy, Graft, Oncology”, Nantes, France
Nantes, Pays de la Loire, France
Carole Guillonneau, n/a

Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France; LabEx IGO “Immunotherapy, Graft, Oncology”, Nantes, France
Nantes, Pays de la Loire, France

The IL-34 cytokine is mainly described for its role in the differentiation and survival of macrophages, and in the regulation of immune responses. We previously showed that IL-34 is also a Treg-secreted cytokine that induces tolerance in conjunction with a sub-optimal dose of rapamycin in a model of rat cardiac allograft, and induces tolerogenic macrophages able to increase CD8⁺ and CD4⁺ Tregs generation in vitro in humans and in vivo in rodents.

Studying the potential of IL-34 as a tool for immunotherapy in transplantation, we described that human IL-34 treatment in combination with a short-term sub-optimal dose of rapamycin efficiently delays acute xenoGvHD development and human skin graft rejection in hPBMC humanized NSG mice.

To improve the potency and/or half-life of IL-34 in vivo, modifications were introduced in the IL-34 structure, either by mutations in key residues of the IL-34 sequence or by producing an IL-34-Fc fusion protein. The capacity of IL-34 mutants to induce monocyte differentiation and activation was then evaluated. In a flow-cytometric assay, increased levels of pAkt and pERK1/2 were observed for some mutants following CSF-1R signalling. Furthermore, monocytes treated with some of these IL-34 mutants showed a tolerogenic phenotype and a better survival at lower concentrations in viability assays.

Treatment of NSG mice with the different variants is under way in our models. Altogether, wild-type and mutated IL-34 have potential to be used in immunotherapy.