CRISPR-Cas9: what is beyond cancer immunotherapy?

Document Type : Review Article

Authors

1 Internal Medicine Department, medical oncology unit, Oncology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt

2 1-Mansoura Manchester Medical Program, Faculty of Medicine, Mansoura University, Mansoura, Egyp

Abstract

Background: Cancer immunotherapy has generated several breakthroughs in targeted therapy; it has been vital for understanding and treating many previously treatment-resistant cancer patients as human papilloma virus (HPV) vaccination and genetic editing of the individual’s immune cells in what is known as adoptive cell transfer (ACT). CRISPR/Cas9 discovery has been ground breaking in the gene-editing industry given its simplicity and ability to genetically edit several genes simultaneously. Current application of autologous chimerically activated receptors (CAR) T cells has proven to be beneficial for several leukemia and multiple myeloma patients but faces several obstacles and limitations.

Purpose: In this article, we explore several approaches by which CRISPR/Cas 9 can edit immune cells to generate more diverse and broad application of adoptive cell transfer.

Summary of the findings CRISPR/Cas9 could potentially generate allogenic CAR-T cells through knocking out TCR and human leucocytic antigen (HLA) molecules on the transfused immune cells thereby preventing graft vs host disease (GVHD) and rejection, respectively. Moreover, CRISPR/Cas9 can generate safe CAR-T cells by preventing cytokine release storm (CRS).

Conclusion Combining these two revolutionary concepts, CRISPR/Cas9 and immunotherapy, can allow us to more broadly apply immunotherapy and deliver it to more cancer patients. There are several proposed advantages and implications of using CRISPR/Cas 9 as a gene editing tool to produce “off the shelf” immune cells that are both effective and safe

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