Past, Present and Future of Engineered Cell Therapy

Engineered cell therapy is an emerging field of science to target and treat cancer. Current strategies include utilizing immune cells such as T cells, NK cells and Macrophages or other cells such as RBC, induced pluripotent stem cells. These cells are genetically engineered to express tumor antigen-specific protein on the cell surface along with gene modifications to make these cells more tolerant and persist longer in the patient. The field is moving towards combination therapy and making marked improvements in manufacturing and logistics of this therapy. Combination therapy include CAR-T cells with immune modulators such as PD-1 inhibitors or with other cell therapies such as CAR-NK cells. Manufacturing improvements include shortening the culture period thereby reducing the time from bench-to-bedside, making the cells off-the-shelf (allogeneic) and logistics of sourcing raw materials. Gene modification technologies including CRISPR, zincfinger, MegaTALs can knockdown genes that can cause graft versus host disease and knock-in genes that encode for CAR or factors such as cytokines that increase the persistence of these cells. Despite these scientific advancements, we are still at the beginning of these therapeutic milestones. Targeting solid tumor with this therapy has been a challenge and modulating the tumor microenvironment to accentuate the function of CAR-cells are being explored.

Learning objectives:

1. Understand the gene engineered cell therapy field

2. Areas that need improvement in this field

3. Manufacturing objectives in cell therapy