Trivalent CAR-T Cells for Targeting of Cancerous Hematopoietic Cells

Stanford scientists have developed a trivalent CAR T cell that targets three proteins that are essential for self-renewal and differentiation of leukemic stem cells. These CAR T cells can also effectively traffic to the bone marrow by overexpressing a relevant chemokine receptor. The use of these CAR T cells to treat acute myeloid leukemia could enable full disease eradication.

Leukemia is one of the most common types of cancers in children and teens, but disease outcomes are generally poor with a survival rate of ~50% and disease relapse being a common issue. A reason for high relapse rates with current therapies is the persistence of residual cell with tumor-initiating capacity, often referred to as leukemic stem cells. These cells have been shown to perpetuate and maintain leukemia and standard chemotherapies that target leukemia tend to minimally effect leukemic stem cells. Hence, new therapies that can target leukemic stem cells are necessary to improve leukemia outcomes and enable full disease eradication.

A trivalent CAR T cell that overexpresses a chemokine receptor to enhance targeting to the bone marrow was developed that showcased broad cytotoxicity to leukemia cell lines. Importantly, the trivalent CAR T cells could also kill hematopoietic stem cells and progenitors, leukemic stem cells, and leukemic blasts in vitro. Consequently, this establishes proof-of-concept that a trivalent CAR T cell can be utilized to eradicate leukemia in cancer patients.

Stage of Development:
Pre-clinical