Background Compared to normal cells or their corresponding tissues, CD200 is overexpressed in various cancers such as kidney cancer, head and neck cancer, and colon cancer. The upregulation of CD200 on various human cancer cells has an immunosuppressive effect on immune cells within the tumor microenvironment, creating conditions that favor tumor development, growth, and spread. This indicates that CD200 is a potential therapeutic target and prognostic factor for a range of malignant tumors.

Methods To evaluate the preclinical efficacy of therapies targeting CD200 or CD200R, we developed a human CD200 and CD200R in situ knock-in (B-hCD200/hCD200R) mouse model and a human CD200 in situ knock-in (B-hCD200 MC38) murine colon cancer cell line. We used flow cytometry to assess the protein expression of CD200 and CD200R in B-hCD200/hCD200R mice, as well as the CD200 protein expression on B-hCD200 MC38 cells. We established a syngeneic mouse model by inoculating B-hCD200 MC38 cells into B-hCD200/hCD200R mice and measured the tumor growth curve. Our collaborative client evaluated the pharmacodynamics of an anti-human CD200 antibody combined with an anti-mouse PD-1 antibody in this model.

Results We confirmed the expression of human CD200 and CD200R proteins in B-hCD200/hCD200R mice, as well as high levels of human CD200 protein expression in B-hCD200 MC38 cells. In vivo tumor growth was comparable between B-hCD200 MC38 and wild-type MC38 cells in B-hCD200/hCD200R mice. The combination of an anti-human CD200 antibody and an anti-mouse PD-1 antibody effectively inhibited the growth of B-hCD200 MC38 tumors in B-hCD200/hCD200R mice.

Conclusions B-hCD200/hCD200R mice and B-hCD200 MC38 cells can be paired to evaluate the in vivo efficacy of anti-human CD200 antibodies and immune checkpoint drugs.