NK cell-based therapies for HIV infection: Investigating current advances and future possibilities

NK cells are well-known for their antiviral functions. Also, their role in HIV has been well established, with rapid responses elicited during early HIV infection. Most immune cells including CD4⁺ T cells, monocytes, Mϕs, and dendritic cells are readily infected by HIV. Recent evidence from multiple studies has suggested that similar to these cells, in chronic conditions like HIV, NK cells also undergo functional exhaustion with impaired cytotoxicity, altered cytokine production, and impaired ADCC. NK-based immunotherapy aims to successfully restore, boost, and modify their activity as has been already demonstrated in the field of cancer immunotherapy. The utilization of NK cell-based strategies for the eradication of HIV from the body provides many advantages over classical ART. The literature search consisted of manually selecting the most relevant studies from databases including PubMed, Embase, Google Scholar, and ClinicalTrial.gov. Some of the treatments currently under consideration are CAR-NK cell therapy, facilitating ADCC, TLR agonists, bNAbs, and BiKEs/TriKEs, blocking inhibitory NK receptors during infection, IL-15 and IL-15 superagonists (eg: ALT-803), and so on. This review aims to discuss the NK cell-based therapies currently under experimentation against HIV infection and finally highlight the challenges associated with NK cell-based immunotherapies.