%0 Journal Article
%T Fully murine CD105-targeted CAR-T cells provide an immunocompetent model for CAR-T cell biology.
%A Lontos K
%A Wang Y
%A Colbert M
%A Kumar A
%A Joshi S
%A Philbin M
%A Wang Y
%A Frisch A
%A Lohmueller J
%A Rivadeneira DB
%A Delgoffe GM
%J Oncoimmunology
%V 11
%N 1
%D 2022
%M 36275862
暂无%R 10.1080/2162402X.2022.2131229
%X 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 TGFβ 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.