All about Natural Killer Cells (NKs)

Montreux, Switzerland | March 31, 2021 – NK cells were first identified in the 1960s and within 10 years researchers began to explore this previously unknown population of innate lymphocytes, now referred to as natural killer (NK) cells.

The existence of natural cytotoxic lymphocytes, also known as natural killer (NK) cells, with intrinsic and innate cell killing properties was discovered in experiments with T cells. As their name suggests, NK cells are constitutively cytotoxic and, unlike cytotoxic T cells, do not require prior exposure to an antigen to activate their cell killing effects. NK cell activity was first observed in the mononuclear cell population of human peripheral blood; however, this cell type resides in several lymphoid and non-lymphoid tissues, including bone marrow, lymph nodes, skin, intestine, tonsils, liver, and lung.

In terms of cytotoxicity, the fundamental difference between cytotoxic (CD8+) T cells and NK cells is that the CD8+ T cell requires activation by a helper (CD4+) T cell to express its cytotoxicity. NK cell receptors are synthesised during cell development and maturation. NK cells use innate receptors (such as immunoglobulin receptors) to grow, mature, and recognise their environment.

NK cells are large granular lymphocytes (as opposed to “small lymphocytes”), they do not express the markers characteristics of T or B cells (CD3 and CD19), in humans NK cells are characterised by the markers CD56, CD16, and of course NK. These cells account for approximately 5-20% of human lymphocytes and belong to the innate immune system due to their invariant non-adaptive receptors.

It was originally thought that NK cells develop exclusively in the bone marrow. However, recent evidence in humans and mice suggests that they can also develop and mature in secondary lymphoid tissues including the tonsils, spleen, and lymph nodes. The cell progenitors and intermediate populations that give rise to NK cells are defined by the differential expression of lineage-specific surface markers.

Natural killer cells mediate their effects through two essential effector functions. NK cells are cytotoxic lymphocytes that can directly lyse cells that have undergone malignant transformation or that have been infected by a virus or other intracellular pathogen.

The cytolytic function of NK cells can be initiated through a variety of processes, including de-granulation and stimulation of death receptors, and is essential in the normal physiology for the removal of diseased and dysfunctional cells. Second, NK cells can produce a variety of inflammatory cytokines in response to receptor stimulation and inflammatory cytokine-induced activation. These effector functions of NK cells are essential components of the immune response and are the main mechanisms by which NK cells provide function as part of the immune system.

NK cells are interesting candidates for immunotherapy due to their innate and independent cell killing capability, their suitability for collection, expansion and storage, and the ability to direct them towards specific target cells.  The use of allogeneic NK cells can provide an additional functional immune capacity in a patient, and this can be especially effective in pathologies that are compromising the host immune system.  In addition, NK therapy has a lower risk of engendering new stimulation or over-stimulation of host immune mechanisms which are an unfortunate side-effect of several current cellular immunotherapy methods.

The MedXCell Group is developing new therapeutic products based on formulations containing allogeneic human NK cells.  These products will take advantage of natural ability of NK calls to act as cytotoxic agents as well as the ability of monoclonal antibodies and other ligands to direct the NK cell cytotoxicity to populations of cells responsible for pathology.  Envisaged indications include oncology, autoimmunity and infectious disease.

The MedXCell Group expects to be able to establish rapidly a platform to underpin the development of products for multiple indications using a single population of NK cells.  This population of cells will not undergo modification and will be passively armed using indication-specific ligands to recognize target cells.

In this way, the MedXCell Group platform will serve as a “toolkit” for the rapid formulation and validation of new cell targets for immunotherapy.

 

For more information, please contact:

Alan Cookson, CTO

+41 21 963 06 53       

alan.cookson@medxcell.ch