Memory and CAR‐NK cell‐based novel approaches for HIV vaccination and eradication

Abstract

Human immunodeficiency virus (HIV) is one of the critical infectious agents with thousands of newly infected people worldwide. High mutational capability and rapid diversification, inhibition of humoral and cellular immune responses, and thus inability for recognition of an immunogenic region in the viral envelope by the immune system are major challenges. Natural killer (NK) cells are multifunctional, playing a key role in the identification and elimination of HIV‐infected cells. These cells identify and eliminate virus‐infected cells in a multilateral manner, such as ligand stress, antibody‐dependent cell cytotoxicity (ADCC), T follicular helper (Tfh), and the activation of most of the stimulatory receptors. Moreover, these cells release cytokines leading to the activation of cytotoxic lymphocytes (CTLs) and dendritic cells (DCs), contributing to efficient viral elimination. Some subsets of NK cells exhibit putatively enhanced effector functions against viruses following vaccination easily expanded and identified by NK cell lines culture. Furthermore, NK cells promote the elimination of HIV‐infected cells which reduce the expression of major histocompatibility complex (MHC) molecules. Memory NK cells have higher functionality and renewable potential. A pioneering strategy to establish an efficacious HIV vaccine would include stimulation of the accumulation and long‐term maintenance of these HIV‐reactive NK cells. CAR‐NK (chimeric antigen receptor‐natural killer) cells‐based antiviral therapies have emerged as novel approaches with the ability of antigen recognition and more advantages than CAR‐T (chimeric antigen receptor‐T) cells. Recent development of induced pluripotent stem cell (iPSC)‐derived NK cells with enhanced activity and efficiency conferred a promising insight into CAR‐NK cell‐based therapies. Therefore, memory and CAR‐NK cells‐based approaches can emerge as novel strategies providing implications for HIV vaccine design and therapy.

Harnessing Memory NK Cell to Protect Against COVID-19

“…In addition, NK cells present in the lung are often enriched in CD56dim/CD16bright cells but recently, during the HCMV infection, a novel adaptive killer-cell Ig-like receptor (KIR)+/NKG2C+/NK cell subset with a CD49a+/CD56bright/CD16- tissue-resident (tr) NK cell phenotype ( Figure 2 ) has been identified in human lungs ( Cong and Wei, 2019 ; Dogra et al., 2020 ). Considering this immunological aspect, the development of trNK cells and the emergence of their adaptive feature have also demonstrated much broader diversity than before, and the generation of different types of long-lived adaptive NK cells has added further attractiveness and complexity to this field ( Freud et al., 2017 ; Mazarzaei et al., 2019 ).…”

“…A significant evolution of cell therapy can be thus represented by NK cells engineered with CAR-targeting antigens (CAR-NK) ( Souza-Fonseca-Guimaraes et al., 2019 ). CAR-NK cells may also characterize an off-the-shelf tool based on viral immunogenic and conserved domains and even applied singly or combined with other therapeutic approaches for viruses ( Mazarzaei et al., 2019 ). Novel strategies can be now used to manipulate NK cell function, targeting their major inhibitory checkpoints ( Bi and Tian, 2019 ) such as KIR ( Pende et al., 2009 ), NKG2A ( André et al., 2018 ), and programmed cell death protein 1 (PD-1) ( Lipson et al., 2013 ).…”

DNAM-1 Activating Receptor and Its Ligands: How Do Viruses Affect the NK Cell-Mediated Immune Surveillance during the Various Phases of Infection?

“…In the context of viral infection, it represents a promising clinical perspective aimed to promote the viral clearance for the cure of immune compromised patients [206] as well as chronically virus-infected patients [207]. Moreover, although it needs still further investigations, the use of chimeric antigen receptor (CAR)-engineered NK cells specifically committed to recognized and kill cells expressing viral proteins represents a novel, fascinating approach [208].…”

Immunotherapy and CRISPR Cas Systems: Potential Cure of COVID-19?

“…CAR-NK cells may also utilized as an off-The-shelf tool alone or in combination with other therapeutic methods for viruses. 155 However, an allogeneic and off-The-shelf NK cell which are cryopreserved, CYNK-001, derived from placental stem cells for treating leukemia and multiple myeloma is manufactured. 156 Also scientists carried out trials to evaluate the effect of CYNK-001 against mild COVID-19.…”