Targeting stimulatory and inhibitory receptor/ligand interactions to diminish human anti-pig immune responses (A01)

• Subject Area: General and Visceral Surgery ; Immunology
• Term: from 2012 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 213602983

It is the aim of this project is to establish conditions leading to strong inhibitory and weak stimulatory signals in human immune cells when they come into contact with porcine cells and tissues. Pigs expressing the human (h) inhibitory ligand hPD-L1 and pigs lacking MHC (SLA, “swine leukocyte antigen”) class-I molecules have been generated. In vitro studies revealed partial protection of hPD-L1-transgenic or SLA class-I-deficient cells from human immune responses. We will now combine the two strategies and expect that hPD-L1pos SLA class-Ineg cells and tissues exhibit particularly low immunogenicity. By SLA-HLA typing and functional testing, porcine SLA alleles with low stimulatory capacity for a prospective recipient will be defined. Together with additional genetic engineering in the course of ex vivo perfusion, these concepts will enable the selection/generation of xenografts that fully match the needs of a specific patient (“personalised grafts”).

• DFG Programme: CRC/Transregios
• Subproject of: TRR 127: Biology of Xenogeneic Cell and Organ Transplantation - From Bench to Bedside
• Applicant Institution: Ludwig-Maximilians-Universität München
• Project Heads: Professorin Dr. Constanca Figueiredo; Dr. Joachim Hundrieser, until 6/2016; Professor Dr. Reinhard Schwinzer