Cd33 Car T Cells

Inactivation of cd33 in hspcs permits cd33 directed car t cell treatment of aml.

Cd33 car t cells.

Cll1 is associated with leukemia stem cells and disease relapse and cd33 is expressed on the bulk aml disease. This is a phase 1 2 trial which aims to determine the safety and feasibility of anti cd33 chimeric antigen receptor car expressing t cells cd33cart in children and adolescents young adults ayas with relapsed refractory acute myeloid leukemia aml. Little difference in tumor cell numbers was apparent when anti cd33 car t cells or vector transduced t cells were co cultured with the cd33. A chimeric antigen receptor expressing t cell that targets and kills cd33 expressing cancers such as acute myeloid leukemia aml.

Cd33 ablated hspcs exhibited normal myeloid function and differentiation in vivo. This concept has been recently successfully demonstrated in preclinical studies of cd19 car t cells and ibrutinib in all flt3 car t cells with the flt3 inhibitor crenolanib in aml and cd33 or cd19 car t cells with the pi3k inhibitor ly294002 in aml and all respectively. These studies illuminate a novel approach to antigen specific immunotherapy by genetically engineering the host to avoid on target off tumor toxicity. The car construct works by using a novel anti cd33 scfv region to enable t cell targeting of cd33 expressing cancer cells and t cell activation through the incorporation of co stimulator and intracellular signaling regions.

Previously we demonstrated the profound anti tumor activity of cll1 cd33 compound car ccar t cells. In response novel bispecific human cd33 123 car t cells with split signaling costimulation domains were highly efficacious in vitro at killing target cells proliferating and generating substantial. Cd33 or cd123 targeted chimeric antigen receptor car t cell therapies have shown promise but struggle with on target off tumor toxicities complicated allogeneic hsc transplants and aml relapse. Cd33 a commonly targeted antigen is expressed in about 85 90 of aml cases but is also present on normal myeloid progenitors and myelocytes.

Cll1 and cd33 are often used as targets for aml car t cell therapy. Cd33 deficient cells were impervious to cd33 targeting car t cells allowing for efficient elimination of leukemia without myelotoxicity. However aml cells lack ideal targeting antigens that are safe to target with car t cells. 59 70 98 finally successful engineering and treatment of patients with.

Our aim was to engineer and validate cd33 directed car t cells with the intention to open a phase i clinical. We show that both these modified t cells are very efficient in reducing leukemia burden in vivo but only the anti cd123 car has limited killing on normal hspcs thus.