Current Status of Gene Engineering Cell Therapeutics

Abstract

Ex vivo manipulations of autologous patient's cells or gene-engineered cell therapeutics have allowed the development of cell and gene therapy approaches to treat otherwise incurable diseases. These modalities of personalized medicine have already shown great promises including product commercialization for some rare diseases. The transfer of a chimeric antigen receptor or T cell receptor genes into autologous T cells has led to very promising outcomes for some cancers, and particularly for hematological malignancies. In addition, gene-engineered cell therapeutics are also being explored to induce tolerance and regulate inflammation. Here, we review the latest gene-engineered cell therapeutic approaches being currently explored to induce an efficient immune response against cancer cells or viruses by engineering T cells, natural killer cells, gamma delta T cells, or cytokine-induced killer cells and to modulate inflammation using regulatory T cells.

Keywords: allogeneic; autologous; cell therapy; ex vivo therapy; gene therapy.

Figure 1

Gene-engineered cell therapeutic approaches are currently explored preclinically and clinically to induce potent immunity against cancer, infection, or to induce tolerance. (A) Different gene-engineered cell therapeutic approaches using either T cells, natural killer (NK) cells, cytokine-induced killer (CIK) cells, or γδ T cells are being explored to induce an efficient immune response against cancer cells. Notably, these different cell types can be reprogrammed by gene transfer of a T cell receptor (TCR) or a chimeric antigen receptor (CAR), so they can target efficiently specific antigens expressed by cancer cells. (B) Virus-specific T cells can be used as a cell therapy approach to restore virus-specific immunity in patients. (C) Different approaches are being explored to induce tolerance for different indications by either using mesenchymal stem cells (MSC), double negative (DN) T cells, CAR T cells, or regulatory T cells (Tregs)-based approaches or by explored manipulating Tregs (CAR-Tregs).