Case Report: Feasibility and Safety of Autologous NK Cell Therapy in Patients with Cancer

This study reported two cases of Thai cancer patients, including a 36-year-old female with thyroid cancer of more than 5 years and a 64-year-old male with lung and colon cancers of more than 10 years. The written informed consent was provided for autologous natural killer (NK) cell infusion at the anti-ageing and regenerative medicines clinic. Briefly, the blood was taken from the patient for NK cell count and their cytotoxic activity. Then, the patient’s NK cells were expanded in vitro, characterized and then counted before being delivered to the same patient by a single intravenous infusion. The vital signs and general physical examinations were observed for 2 - 6 hours after the infusion. The patients were discharged if there were no adverse effects. The data showed the increasing number of NK cells and level of cytotoxic activity after the NK cell treatment, compared to the pre-treatment. In addition, the increasing total live cell concentration, as identified by the high percentage of CD56dim/CD16bright cytotoxic NK cells, at day 21 of the NK cell expansion was consistent with the increasing cytotoxic activity of the patients after the treatment. Here, we demonstrated that this autologous NK cell therapy might be feasible;however, the study did not aim to evaluate the anti-cancer effect.

Engineered human pluripotent stem cell-derived natural killer cells: the next frontier for cancer immunotherapy

Adoptive immunotherapy using immune effector cells has revolutionized cancer treatments with approval of two autologous chimeric antigen receptor(CAR)T cell therapies by the US FDA.Clinical trials using natural killer(NK)cell-based adoptive immunotherapy have been shown to be safe and effective for treatment of multiple malignancies,especially acute myelogenous leukemia.However,most of these trails use primary NK cells isolated from peripheral or cord blood which can have donor-dependent variability and can be challenging to genetic engineer to improve antitumor functions,limiting the widespread use of this promising new therapy.NK cells can now be routinely produced from human pluripotent stem cells,both human embryonic stem cells(hESCs)and induced pluripotent stem cells(iPSCs).These pluripotent stem cells are homogenous,easy to genetically modify on a clonal level and can be used as unlimited source of NK cells,making them ideal population to develop standardized,off-the-shelf adoptive NK cell therapy products.In this review,we discuss recent advances of obtaining and expanding hESC and iPSC-derived NK cells and novel genetic engineering strategies that are being applied to improve their antitumor functions.