Related Experiment Video
Updated: Aug 18, 2026
Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood
Published on: February 5, 2020
PD-1-specific "Blocking" antibodies that deplete PD-1+ T cells present an inconvenient variable in preclinical
Fanny Polesso1, Michael W Munks2, Katherine H Rott2
1Department of Cell, Developmental, & Cancer Biology, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, 97239, USA.
Abstract:
Therapeutic antibodies blocking PD-1-/PD-L1 interaction have achieved remarkable clinical success in cancer. In addition to blocking a target molecule, some isotypes of antibodies can activate complement, NK cells or phagocytes, resulting in death of the cell expressing the antibody's target. Human anti-PD-1 therapeutics use antibody isotypes designed to minimize such antibody-dependent lysis. In contrast, anti-PD-1 reagents used in mice are derived from multiple species, with different isotypes, and are not engineered to reduce target cell death: few studies analyze or discuss how antibody species and isotype may impact data interpretation. We demonstrate here that anti-PD-1 therapy to promote activation and proliferation of murine PD-1-expressing CD8 T cells sometimes led instead to a loss of antigen specific cells. This phenomenon was seen in two tumor models and a model of virus infection, and varied with the clone of anti-PD-1 antibody. Additionally, we compared competition among anti-PD-1 clones to find a combination that allows detection of PD-1-expressing cells despite the presence of blocking anti-PD1 antibodies in vivo. These data bring attention to the possibility of unintended target cell depletion with some commonly used anti-mouse PD-1 clones, and should provide a valuable resource for the design and interpretation of anti-PD-1 studies in mice.
Insights
Some anti-PD-1 antibodies used in mice can deplete target CD8 T cells, unlike human therapeutics. This unintended cell loss varies by antibody clone and impacts research, necessitating careful selection for accurate results.
Area of Science:
- Immunology
- Cancer Biology
- Pharmacology
Background:
- Therapeutic antibodies targeting PD-1/PD-L1 interactions are successful in cancer treatment.
- Human anti-PD-1 antibodies are engineered to minimize antibody-dependent cell lysis.
- Murine anti-PD-1 reagents often lack this engineering, potentially causing unintended effects.
Purpose of the Study:
- To investigate the impact of antibody isotype and species on anti-PD-1 therapy outcomes in mice.
- To identify anti-PD-1 antibody clones that may cause unintended target cell depletion.
- To compare anti-PD-1 clones for detecting PD-1-expressing cells in vivo.
Main Methods:
- Administered various anti-PD-1 antibody clones in murine tumor and viral infection models.
- Assessed CD8 T cell populations and antigen-specific cell survival.
- Evaluated antibody competition for PD-1 binding to optimize detection methods.
Main Results:
- Certain anti-PD-1 antibody clones induced depletion of PD-1-expressing CD8 T cells, contrary to intended activation.
- This unintended cell loss was observed across different models and varied significantly between antibody clones.
- A method for detecting PD-1-expressing cells in the presence of blocking antibodies was developed.
Conclusions:
- Commonly used anti-mouse PD-1 antibodies can cause unintended target cell depletion.
- Antibody clone selection is critical for accurate interpretation of anti-PD-1 studies in mice.
- These findings offer guidance for designing and interpreting preclinical anti-PD-1 research.
More Related Videos
10:18Author Spotlight: Magnetic Fluorescent Bead-Based Dual-Reporter Flow Analysis of PDL1-Vaxx Peptide Vaccine-Induced Antibody Blockade of the PD-1/PD-L1 Interaction
Published on: July 7, 2023
07:04Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology
Published on: May 2, 2025
