Improvement Of CAR-T Therapy with Gene Editing Technologies

In recent decades, after some breakthroughs in field of immunology, the numbers of studies related to cancer immunotherapy are exploding and growing. As a promising branch, adoptive cell therapy, has been shown to have a very high remission rate in patients with hematologic tumors as well as patients with metastatic and multi-therapy resistant melanoma by engineering T cell or natural killer (NK) cells outside the body. CAR-T therapy has gained significant recognition as a cancer treatment due to its exceptional effectiveness in treating hematologic malignancies. Consequently, there are researchers that wish to apply this technology to solid tumor therapy. But throughout this process, some solid tumor traits as well as the therapy's adverse effects constitute a significant challenge. With the advancement of gene editing technology, some researchers are able to alter the structure of CAR-T cells to increase the effectiveness of CAR-T treatment and address some drawbacks, such as the potential to cause GVHD and immunological rejection. Subsequent examples will illustrate this point broadly. By using TALENs to disrupt the TRAC gene or HLA-A locus of the MHC gene complex, the risk of GVHD and immunological rejection can be decreased. CRISPR/Cas9-mediated PD-1 protein knockout can extend the lifespan of CAR-T cells within the body. When toxicity manifests, appropriate staff may be able to eradicate every CAR-T cell in the patient's body by introducing a suicide gene or introducing a safety switch into CAR-T cells using CRISPR.