iPSC-mediated genetic manipulation promotes natural killer cell-centered cancer immunotherapy

Abstract

Natural killer (NK) cells demonstrate potent cytotoxic activities and the capacity to secrete cytokines. Their distinctive capability to trigger cell death, bypassing the need for major histocompatibility complex recognition, opens promising avenues for their use in clinical settings such as allogeneic transplantation and tumor immunotherapy. Although the ability of NK cells to kill hematological tumors has been widely recognized, their effectiveness in treating solid tumors is not as pronounced. The intricate interplay of NK cells with the tumor microenvironment, specifically in the context of solid malignancies, has been noted to attenuate the anti-cancer prowess of NK cells and foster the ability of malignant cells to elude immune surveillance. Successful NK cell-centered immunotherapy hinges on obtaining a substantial quantity of NK cells with potent tumor-killing capabilities. However, the current challenge lies in the limited ex vivo expansion of NK cells and the inefficiency of gene introduction methods. Induced pluripotent stem cells (iPSCs) are multipotent stem cells with relatively easier gene transfection capability and theoretically unlimited proliferation potential. NK cells derived from iPSCs circumvent the challenge of difficult genetic modification in NK cells, offering various potential strategies to counteract the immune suppression induced by the tumor microenvironment.

Keywords

Induced pluripotent stem cells / Natural killer cells / Solid cancer / CAR-NK cells / Immunotherapy