PMC:7324763 / 57942-59755 JSONTXT

{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/7324763","sourcedb":"PMC","sourceid":"7324763","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7324763","text":"Interleukin Therapy and NK Cells\nIn addition to IFN cytokine therapy, interleukin cytokine therapy can enhance the effector functions of NK cells (158). The use of whole, unmodified recombinant cytokines as a monotherapy has resulted in minimal success in humans in cancer immunotherapy. The earliest cytokine therapies to gain FDA-approval were IFN-α and recombinant IL-2, approved for renal cell carcinoma and metastatic melanoma (187). Although approved, they were limited by their in vivo half-life, marginal anti-tumor activity, and associated toxicities. The next generation of cytokine therapies were created to address these issues by first improving their biological stability through pegylation and fusion to chaperone molecules and secondly improving their specificity by fusing cytokines with antibodies or intratumoral administration. These advances in the field have allowed for the reassessment of the therapeutic potential of specific cytokines (187).\nGiven the importance of IL-15 signaling and NK cell function, researchers have developed IL-15 “superagonists” which are IL-15:IL-15R heterodimers that have better in vivo stability and bioactivity compared to monomeric IL-15 (168). Although at the time of writing IL-15 superagonists are not being studied for their efficacy in COVID-19 patients, IL-15 superagonists, such as ALT-803, are safe in humans (188) and have been used in conjunction with many of the therapies being discussed in this review including: CAR-NK cell therapy, adoptive NK cell transfers, checkpoint inhibitors, and the BCG vaccine in cancer (189). It should be noted that although the therapeutic potential of cytokine therapy to specifically stimulate NK cells is enticing, exogenous cytokine therapy has a high risk for exacerbating CRS if given at the incorrect 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