23ME-00610, a genetically informed, first-in-class antibody targeting CD200R1 to enhance antitumor T cell function

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.