全鼠源 CD105 靶向 CAR-T 细胞为 CAR-T 细胞生物学提供免疫健全模型

The modeling of chimeric antigen receptor (CAR) T cell therapies has been mostly focused on immunodeficient models.

However, there are many advantages in studying CAR-T cell biology in an immunocompetent setting.

We generated a fully murine CAR targeting CD105 (endoglin), a component of the TGF receptor expressed on the surface of certain solid tumors and acute leukemias. CD105-targeted CAR-T cells can be grown from various murine backgrounds, tracked in vivo by congenic marks, and be activated by CD105 in isolation or expressed by tumor cells.

CD105-targeted CAR-T cells were toxic at higher doses but proved safe in lower doses and modestly effective in treating wild-type B16 melanoma-bearing mice. CAR-T cells infiltrating the tumor expressed high levels of exhaustion markers and exhibited metabolic insufficiencies.

We also generated a human CD105 CAR, which was efficacious in treating human melanoma and acute myeloid leukemia in vivo .

Our work details a new murine model of CAR-T cell therapy that can be used from immunologists to further our understanding of CAR-T cell biology.

We also set the foundation for further exploration of CD105 as a possible human CAR-T cell target.