Cd33 Car T Cells

In this study we describe the in vivo efficacy and safety of using cytokine induced killer cik cells genetically modified to express anti cd33 or anti cd123 car to target aml.

Cd33 car t cells.

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. 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. 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. 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.

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. Our aim was to engineer and validate cd33 directed car t cells with the intention to open a phase i clinical. Cll1 is associated with leukemia stem cells and disease relapse and cd33 is expressed on the bulk aml disease. Cd33 a commonly targeted antigen is expressed in about 85 90 of aml cases but is also present on normal myeloid progenitors and myelocytes.

Cd33 ablated hspcs exhibited normal myeloid function and differentiation in vivo. Inactivation of cd33 in hspcs permits cd33 directed car t cell treatment of aml. However aml cells lack ideal targeting antigens that are safe to target with car t cells. Gene editing of normal cells is a potential therapeutic approach to generate cancer specific antigens.

Cd33 deficient cells were impervious to cd33 targeting car t cells allowing for efficient elimination of leukemia without myelotoxicity. Previously we demonstrated the profound anti tumor activity of cll1 cd33 compound car ccar t cells. Cll1 and cd33 are often used as targets for aml car t cell therapy. A chimeric antigen receptor expressing t cell that targets and kills cd33 expressing cancers such as acute myeloid leukemia aml.

Anti cd33 car or vector transduced t cells were co cultured with cd33 modified or cd33 parental cell lines at an e t ratio of 1 2 and viable tumor cells were determined by quantitative flow cytometry. 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.