Author(s) :

Vivan Patel.

Volume/Issue :

Abstract :

Multiple myeloma (MM) is an incurable cancer that manifests within the bone marrow, affecting plasma cells. Although incidence and prevalence rates remain low, there has been a gradual increase worldwide in the incidence rates of MM over the past few decades. In the tumor microenvironment, plasma cells undergo mutations during development, leading to uncontrolled cell growth in the bone marrow and the production of abnormal monoclonal antibodies. These malignant plasma cells downregulate the T cell response via upregulated signaling pathways associated with the PDCD1, HAVCR2, and LAG3 genes in T cells. To reinvigorate deactivated T cells, this proposal puts forward an evidence-based approach that uses CRISPR-Cas9 to knock out the PDCD1, HAVCR2, and LAG3 genes in T cells to restore T cell cytotoxic functions against MM. Multiplex gene editing appears promising; however, additional research is required to fully encapsulate the complex nature of their interactions with MM. Since many cancers persist through the activation of redundant signaling pathways that are co-expressed, editing three genes simultaneously is essential to preventing MM from surviving or adapting through alternate pathways. This CRISPR-Cas9-based approach holds immense potential to advance patient outcomes through ex vivo T cell editing, but also raises considerations regarding the effectiveness of triple gene knockout. This proposal discusses in vivo and in vitro research that support such treatment, along with future considerations of coupling CRISPR-Cas9 with other known MM treatment mechanisms.