Natural killer cells: Looking good for cancer therapy
Source: Drug Target Review, November 2023
The suitability of NK cells for cancer therapy has been challenged by some investor and business interests because of limited efficacy data, but is this belief at the present stage of development of the immune therapy field?
NK cells are among the front line of protection from infected and abnormal cells as part of the ‘innate immune response’. They recognise ‘cell stress molecules’ on the surface of infected, old, injured and cancerous cells without the need for complex pre-stimulation signals of the adaptive immune system (eg, T cells). They do not induce ‘graft versus host’ disease when transplanted for allogeneic therapy and there appears little sign of immune rejection.
NK cells can be readily extracted from umbilical cord blood or peripheral blood of adult donors. They may also be derived from induced pluripotent stem cells (iPSCs) made from blood leukocytes or cells of adult tissues. iPSCs are pluripotent, immortal, and may be directed into any cell of the body. NK cells can be manufactured in great abundance from iPSCs in three broad stages: (i) patterning of iPSC into CD34+ cells in 3D bioreactors; (ii) differentiation into NK cells; (iii) numerical expansion and functional maturation under a milieu of growth factors and cytokines. iPSCs may also be gene edited to insert chimeric antigen receptors (CARs) and other enhancers of function and block genes that are part of the inhibition of immune function (frequently used by solid tumours to block killing function of immune cells).