Aptamer-engineered NK cells as immunotherapy against cancer

Natural killer (NK) cells are lymphocytes that innately recognize cancer cells through different receptors expressed on their surface that bind cancer-expressed ligands. However, NK cells miss cell-specific receptors that specifically recognize tumor cells without interfering with normal ones, which are essential in cancer immunotherapy. To overcome this problem, techniques involving genetic manipulation were explored. Nevertheless, they are costly and time-consuming. Moreover, genetic alterations or cell damage could be induced by modifying the DNA. Thus, aptamers which do not involve genetic manipulation, have been used. They are short, single-stranded oligonucleotides that bind with high affinity and specificity to their target molecules, thanks to their 3D structure. Aptamer-engineered NK cells target specific molecules on the cancer cell surface that are not expressed in normal cells. Aptamer-engineered NK cells may be created through different methods. For instance a DNA monomer can be displayed on the cell surface to support aptamers. In this way, it is possible to engineer more than one aptamer on their surface, thus creating polyvalent aptamer mimic (PAM) NK cells. These structures show an improvement in binding and killing target cells than single aptamer engineered NK cells. Another method takes advantage of lipophilic anchors, such as the double-C18 hydrocarbon chain, that allow engineering aptamers on the NK cell surface and stabilize the cells. A major problem in immunotherapy is the capability of immune cells to enter solid tumors, leading to slight therapeutic efficiency. So aptamer-engineered NK cells are investigated in this field. Results show that they successfully penetrate the tumor microenvironment and decrease its volume by killing cancer cells in vitro and in vivo. Thus, compared to native NK cells, these engineered lymphocytes show high efficiency in binding and killing tumor cells. In contrast, they have slight toxicity in normal ones. Moreover, major organs do not show any toxicity compared to control ones. In conclusion, aptamer-engineered NK cells can be a successful immunotherapy technique against cancer.