Harnessing features of adaptive NK cells to generate iPSC-derived NK cells for enhanced immunotherapy.

Select subsets of immune effector cells have the greatest propensity to mediate antitumor responses. However, procuring these subsets is challenging, and cell-based immunotherapy is hampered by limited effector-cell persistence and lack of on-demand availability. To address these limitations, we generated a triple-gene-edited induced pluripotent stem cell (iPSC). The clonal iPSC line was engineered to express a high affinity, non-cleavable version of the Fc receptor CD16a and a membrane-bound interleukin (IL)-15/IL-15R fusion protein. The third edit was a knockout of the ecto-enzyme CD38, which hydrolyzes NAD+. Natural killer (NK) cells derived from these uniformly engineered iPSCs, termed iADAPT, displayed metabolic features and gene expression profiles mirroring those of cytomegalovirus-induced adaptive NK cells. iADAPT NK cells persisted in vivo in the absence of exogenous cytokine and elicited superior antitumor activity. Our findings suggest that unique subsets of the immune system can be modeled through iPSC technology for effective treatment of patients with advanced cancer.

Ethical aspects of urinary diversion for women with irreparable obstetric fistulas in developing countries.

Obstetric fistula formation is a catastrophic complication of prolonged obstructed labor. Obstetric fistulas are common in impoverished countries where access to maternal health care is poor. Although most fistulas can be closed successfully at the time of operation, a small number of women sustain such extensive pelvic injuries that their fistulas are irreparable. Some Western surgeons visiting African countries where fistulas are prevalent have become enthusiastic advocates of performing urinary diversions on these women, transplanting the ureters into the colon. We present a case study of one such woman with an irreparable obstetric fistula and discuss the complex ethical issues involved in considering whether to offer operations of this kind to African fistula victims.