A New Specific Promoter Allow Hematopoietic Stem Cell Immunotherapy Approach Against Acute Lymphoblastic Leukemia Using Chimeric Antigen Receptor

Although efficient, Chimeric Antigen Receptor (CAR)-T cells therapy still presents several drawbacks including exhaustion and loss of engineered cells, and the cytokine release syndrome. To circumvent these issues, we envisioned to engineer hematopoietic stem cells (HSCs) to provide a continuous replenishment of CAR-T and CAR-NK cells. However, this would result in a potentially dangerous pan-hematopoietic expression of the CAR transgene. To avoid this, we designed a T-cell specific and a NK-cell specific synthetic promoter in order to restrict the CAR expression only to the cytotoxic cells progeny issued from CAR-modified HSCs. We assessed the efficacy of our promoters in vitro and in vivo in humanized mice.