NATURAL KILLER CELLS

The natural killer cell constitute 5%–10% of lymphocytes in human peripheral blood, do not express the membrane molecules and receptors that distinguish T- and B-cell lineages. It displays cytotoxic activity against a wide range of tumour cells in the absence of any previous immunization with the tumour.
NK cells were first noticed for their ability to kill tumour cells without any priming or prior activation (in contrast to cytotoxic T cells, which need priming by antigen presenting cells). Additionally, NK cells secrete cytokines such as IFNγ and TNFα, which act on other immune cells like Macrophage and Dendritic cells to enhance the immune response.

Most normal healthy cells express MHC I receptors which mark these cells as ‘self’. Cancer cells and infected cells often lose their MHC I, leaving them vulnerable to NK cell killing. Once the decision is made to kill, the NK cell releases cytotoxic granules containing perforin and granzymes, which leads to lysis of the target cell.
As NK cells can respond to the stimulation within hours without pre-immunization, it is commonly regarded as the first-line fighter against cancer.

Individuals with higher levels of NK cell activity have a low incidence of cancer, proving the potent immunosurveillance ability of NK cells. NK cells are essential in resisting carcinogenesis, although they have poor infiltration and lower cytotoxic ability in the tumour microenvironment (TME).
Decreased frequency of NK cell was found to be associated with higher risk of cancer and worse clinical outcome.

As the development and progression of cancer are correlated with the dysfunction of NK cells, enhancing the function of NK cells is necessary for anti-cancer immunity.

Methods of Enhancing the activity or number of NK CELL: Autologous NK cell enrichment: Unmodified, activated autologous NK cells CAR-NK cell development to overcome the immunosuppressive feature of TME NK cell activation through the major activating receptor NKG2D Activate NK cells using small molecules or cytokines Genetically modified living NK cells Stimulation the body’s natural killer (NK) cells with nanoparticles to increase their numbers and killing ability Allogeneic NK cells UCB-derived NK cells.

Autologous nk cell enrichment involves isolation nk cell susety from blood and then culture expanding culture bag system to increase the number many fold and finally infusing back to the patient, The results demonstrated that NK cells can be harnessed and expanded in vitro and keep the cytotoxicity after the transfer.
peripheral blood mononuclear cell (PBMC) received two infusions, given 48 h apart. The dose of 10(10) cells/m(2) no unexpected NK cell infusion-related toxicity was observed.
Expanded NK cells to almost 4,720-fold. Naturally, NK cells survive for 2 weeks, but the infusion of IL-2 and/or IL-15 showed advantageous effects on the NK cell survival.