Development of anti-feline PD-1 antibody and its functional analysis

Sci Rep. 2023 Apr 24;13(1):6420. doi: 10.1038/s41598-023-31543-6.

Abstract

Antibodies against immune checkpoint molecules restore T-cell function by inhibiting the binding of PD-1 and PD-L1 and have been shown to exert therapeutic effects in various human cancers. However, to date, no monoclonal antibody that recognizes feline PD-1 or PD-L1 has been reported, and there are many unknowns regarding the expression of immune checkpoint molecules and their potential as therapeutic targets in cats. Here we developed anti-feline PD-1 monoclonal antibody (1A1-2), and found that the monoclonal antibody against anti-canine PD-L1 (G11-6), which was previously developed in our laboratory, cross-reacted with feline PD-L1. Both antibodies inhibited the interaction of feline PD-1 and feline PD-L1 in vitro. These inhibitory monoclonal antibodies augmented the interferon-gamma (IFN-γ) production in activated feline peripheral blood lymphocytes (PBLs). Furthermore, for clinical application in cats, we generated a mouse-feline chimeric mAb by fusing the variable region of clone 1A1-2 with the constant region of feline IgG1 (ch-1A1-2). Ch-1A1-2 also augmented the IFN-γ production in activated feline PBLs. From this study, 1A1-2 is first anti-feline PD-1 monoclonal antibody with the ability to inhibit the interaction of feline PD-1 and PD-L1, and the chimeric antibody, ch-1A1-2 will be a beneficial therapeutic antibody for feline tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • B7-H1 Antigen* / metabolism
  • Cats
  • Dogs
  • Humans
  • Immune Checkpoint Proteins / metabolism
  • Mice
  • Neoplasms* / metabolism
  • Programmed Cell Death 1 Receptor / metabolism
  • T-Lymphocytes

Substances

  • B7-H1 Antigen
  • Programmed Cell Death 1 Receptor
  • Immune Checkpoint Proteins
  • Antibodies, Monoclonal