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Updated: Jul 27, 2025
Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
Published on: May 16, 2020
23ME-00610, a genetically informed, first-in-class antibody targeting CD200R1 to enhance antitumor T cell function
Jill Fenaux1, Xin Fang2, Yao-Ming Huang3
1Immuno-Oncology, 23andMe, South San Francisco, CA, USA.
Abstract:
Immune checkpoint inhibition (ICI) has revolutionized cancer treatment; however, only a subset of patients benefit long term. Therefore, methods for identification of novel checkpoint targets and development of therapeutic interventions against them remain a critical challenge. Analysis of human genetics has the potential to inform more successful drug target discovery. We used genome-wide association studies of the 23andMe genetic and health survey database to identify an immuno-oncology signature in which genetic variants are associated with opposing effects on risk for cancer and immune diseases. This signature identified multiple pathway genes mapping to the immune checkpoint comprising CD200, its receptor CD200R1, and the downstream adapter protein DOK2. We confirmed that CD200R1 is elevated on tumor-infiltrating immune cells isolated from cancer patients compared to the matching peripheral blood mononuclear cells. We developed a humanized, effectorless IgG1 antibody (23ME-00610) that bound human CD200R1 with high affinity (KD <0.1 nM), blocked CD200 binding, and inhibited recruitment of DOK2. 23ME-00610 induced T-cell cytokine production and enhanced T cell-mediated tumor cell killing in vitro. Blockade of the CD200:CD200R1 immune checkpoint inhibited tumor growth and engaged immune activation pathways in an S91 tumor cell model of melanoma in mice.
Insights
Genetic analysis identified the CD200:CD200R1 pathway as a novel immune checkpoint target. Blocking this target with antibody 23ME-00610 enhanced anti-tumor immunity and reduced tumor growth in preclinical models.
Area of Science:
- Immunology
- Oncology
- Genetics
Background:
- Immune checkpoint inhibition (ICI) has transformed cancer therapy, but limited patient response necessitates new target discovery.
- Human genetics offers a powerful approach for identifying novel drug targets in immuno-oncology.
Purpose of the Study:
- To identify novel immune checkpoint targets using human genetic data.
- To develop and evaluate a therapeutic antibody against a newly identified checkpoint, CD200:CD200R1.
Main Methods:
- Genome-wide association studies (GWAS) on the 23andMe database to find immuno-oncology signatures.
- Confirmation of CD200R1 expression on tumor-infiltrating immune cells.
- Development of a humanized antibody (23ME-00610) targeting CD200R1.
- In vitro and in vivo studies assessing antibody efficacy in blocking the CD200:CD200R1 pathway and anti-tumor activity.
Main Results:
- GWAS identified an immuno-oncology signature involving CD200, CD200R1, and DOK2.
- CD200R1 was upregulated on tumor-infiltrating immune cells.
- The antibody 23ME-00610 effectively blocked CD200 binding, inhibited DOK2 recruitment, and enhanced T-cell responses.
- CD200:CD200R1 blockade demonstrated anti-tumor effects in a murine melanoma model.
Conclusions:
- The CD200:CD200R1 axis represents a promising novel immune checkpoint for cancer therapy.
- Genetic insights can effectively guide the discovery of new immuno-oncology targets.
- The developed antibody 23ME-00610 shows therapeutic potential for enhancing anti-tumor immunity.
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