LIS1, a glyco-humanized swine polyclonal anti-lymphocyte globulin, as a novel induction treatment in solid organ transplantation

Anti-thymocyte or anti-lymphocyte globulins (ATGs/ALGs) are immunosuppressive drugs used in induction therapies to prevent acute rejection in solid organ transplantation. Because animal-derived, ATGs/ALGs contain highly immunogenic carbohydrate xenoantigens eliciting antibodies that are associated w...

Full description

Saved in:
Bibliographic Details
Published in:Frontiers in immunology 2023-02, Vol.14, p.1137629-1137629
Main Authors: Rousse, Juliette, Royer, Pierre-Joseph, Evanno, Gwénaëlle, Lheriteau, Elsa, Ciron, Carine, Salama, Apolline, Shneiker, Françoise, Duchi, Roberto, Perota, Andrea, Galli, Cesare, Cozzi, Emmanuele, Blancho, Gilles, Duvaux, Odile, Brouard, Sophie, Soulillou, Jean-Paul, Bach, Jean-Marie, Vanhove, Bernard
Format: Article
Language:English
Subjects:
Animals
anti-lymphocyte antibody
anti-lymphocyte globulin
B-Lymphocytes
Globulins
Immunology
induction
kidney trans plantation
Life Sciences
Lymphocytes
Organ Transplantation
polyclonal antibodies (PAbs)
Rabbits
solid organ transplantation
Swine
Transplantation, Homologous
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Anti-thymocyte or anti-lymphocyte globulins (ATGs/ALGs) are immunosuppressive drugs used in induction therapies to prevent acute rejection in solid organ transplantation. Because animal-derived, ATGs/ALGs contain highly immunogenic carbohydrate xenoantigens eliciting antibodies that are associated with subclinical inflammatory events, possibly impacting long-term graft survival. Their strong and long-lasting lymphodepleting activity also increases the risk for infections. We investigated here the and activity of LIS1, a glyco-humanized ALG (GH-ALG) produced in pigs knocked out for the two major xeno-antigens αGal and Neu5Gc. It differs from other ATGs/ALGs by its mechanism of action excluding antibody-dependent cell-mediated cytotoxicity and being restricted to complement-mediated cytotoxicity, phagocyte-mediated cytotoxicity, apoptosis and antigen masking, resulting in profound inhibition of T-cell alloreactivity in mixed leucocyte reactions. Preclinical evaluation in non-human primates showed that GH-ALG dramatically reduced CD4 (p=0.0005,***), CD8 effector T cells (p=0.0002,***) or myeloid cells (p=0.0007,***) but not T-reg (p=0.65, ns) or B cells (p=0.65, ns). Compared with rabbit ATG, GH-ALG induced transient depletion (less than one week) of target T cells in the peripheral blood (
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2023.1137629