Overexpression of NKG2D and IL24 in NK Cell-Derived Exosomes for Cancer Therapy

Natural killer (NK) cell-derived exosomes (NK-Exos) are emerging as a promising avenue in cancer immunotherapy due to their inherent tumor-targeting properties and their capacity to deliver therapeutic agents directly to malignant cells. This research delves into the boosted anti-tumor potency of NK-Exos that has been genetically enhanced to overexpress NKG2D, a vital activating receptor, along with interleukin-24 (IL24), a cytokine renowned for its selective suppressive impact on tumor cells. NKG2D facilitates the recognition of tumor cells by binding to stress-induced ligands, while IL24 induces apoptosis and modulates immune responses to enhance tumor destruction. The NK-Exos engineered to express both NKG2D and IL24 significantly enhanced tumor targeting and increased the apoptosis rate of tumor cells by 30% in A549 and by 20% in HELA at 48 h compared with non-modified NK-Exos, respectively. Furthermore, this enhancement also impacted cell proliferation, with inhibition rates increasing by 30%, 15%, and 15% in A549, HELA, and MCF-7 cells, respectively, and it reduced A549 cell migration by 10%. The integration of NKG2D and IL24 within NK-Exos confers a dual therapeutic mechanism, synergistically amplifying their efficacy in cancer treatment. The utility of NK-Exos co-expressing NKG2D and IL24 offers a novel approach to overcome the limitations of current therapies, providing prolonged tumor suppression and precise targeting of malignant cells and holding great promise for clinical application.