Development and characterization of monoclonal antibodies against canine PD-1 and PD-L1

Yuki Nemoto1, Kazuha Shosu1, Masaru Okuda2

  • 1Laboratory of Molecular Diagnostics and Therapeutics, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi, 753-8515, Japan.

Insights

New monoclonal antibodies targeting the programmed death-1/programmed death ligand 1 (PD-1/PD-L1) pathway in dogs show promise for cancer immunotherapy. These antibodies successfully blocked PD-1/PD-L1 interactions and enhanced T cell activity.

Area of Science:

  • Veterinary Immunology
  • Cancer Immunotherapy
  • Monoclonal Antibody Development

Background:

  • The programmed death-1/programmed death ligand 1 (PD-1/PD-L1) pathway is a key target in cancer immunotherapy.
  • Understanding the PD-1/PD-L1 pathway in canine immune responses is crucial for developing veterinary cancer treatments.

Purpose of the Study:

  • To develop and characterize monoclonal antibodies targeting canine PD-1 and PD-L1.
  • To investigate the expression of PD-1 and PD-L1 on canine immune cells.
  • To evaluate the functional impact of PD-1/PD-L1 blockade on canine T cells.

Main Methods:

  • Development of monoclonal antibodies specific to canine PD-1 and PD-L1.
  • Assessment of antibody binding to cells overexpressing PD-1 and PD-L1.
  • Analysis of PD-1 and PD-L1 expression on activated T cells and immature dendritic cells from canine peripheral blood mononuclear cells (PBMC).
  • Measurement of Interferon-gamma (IFN-γ) production by activated T cells upon antibody treatment.

Main Results:

  • Canine PD-1 and PD-L1 specific monoclonal antibodies were successfully developed.
  • Antibodies demonstrated specific binding to target cells and inhibited PD-1/PD-L1 interactions.
  • PD-1 and PD-L1 expression was confirmed on activated canine T cells; PD-L1 was also detected on immature dendritic cells.
  • Treatment with anti-PD-1 and/or anti-PD-L1 antibodies significantly increased IFN-γ production by activated T cells.

Conclusions:

  • The developed antibodies are effective tools for studying the canine immune system.
  • These antibodies represent a potential first-in-class passive immunotherapy for canine cancer.
  • Further research into PD-1/PD-L1 blockade could advance canine cancer treatment strategies.

Related Concept Videos

PD Controller: Design01:26

PD Controller: Design

In automotive engineering, car suspension systems often employ Proportional Derivative (PD) controllers to enhance performance. PD controllers are utilized to adjust the damping force in response to road conditions. A controller, acting as an amplifier with a constant gain, demonstrates proportional control, with output directly mirroring input.
Designing a continuous-data controller requires selecting and linking components like adders and integrators, which are fundamental in Proportional,...
662
Time-Domain Interpretation of PD Control01:07

Time-Domain Interpretation of PD Control

Proportional-Derivative (PD) control is a widely used control method in various engineering systems to enhance stability and performance. In a system with only proportional control, common issues include high maximum overshoot and oscillation, observed in both the error signal and its rate of change. This behavior can be divided into three distinct phases: initial overshoot, subsequent undershoot, and gradual stabilization.
Consider the example of control of motor torque. Initially, a positive...
408
Frequency-Domain Interpretation of PD Control01:24

Frequency-Domain Interpretation of PD Control

Proportional-Derivative (PD) controllers are widely used in fan control systems to improve stability and performance. A fan control system can be effectively represented using a Bode plot to illustrate the impact of a PD controller through its transfer function. The Bode plot visually conveys how PD control modifies the fan's response across various frequencies, providing a frequency domain interpretation of the controller's behavior.
The proportional control gain, combined with the...
394
Piaget's Stage 1 of Cognitive Development01:14

Piaget's Stage 1 of Cognitive Development

The sensorimotor stage, the initial phase of Jean Piaget's theory of cognitive development, spans the first two years of a child's life. During this period, infants actively engage with their surroundings, building cognitive awareness through direct interaction with the world. This interaction is primarily based on sensory perception and motor actions, allowing infants to gradually understand basic physical properties and predict how objects interact within their environment.
Exploration...
1.9K
Antibody Structure01:10

Antibody Structure

Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
65.7K
Antibody Actions01:26

Antibody Actions

Antibodies, or immunoglobulins, are critical players in the immune system's arsenal against invading pathogens. Produced by B cells and plasma cells, their primary role is to detect and bind to specific antigens, molecules found on the surface of pathogens like bacteria or viruses. Beyond antigen recognition, antibodies perform several vital functions that contribute to immune defense.
Neutralization
Antibodies can bind to pathogens, preventing them from infecting host cells. This process...
2.9K