Clinical-Scale NK Cells for Cancer Therapy Made from Pluripotent Stem Cells


Dan Kaufman’s laboratory has done it again. The Kaufman laboratory at the University of Minnesota in collaboration with scientists from MD Anderson Cancer Center in Houston, Texas have designed a protocol to make natural killer cells from embryonic stem and induced pluripotent stem cells.

Natural killer cells provide a very important contribution to the innate immune response. These cells produce molecules called cytokines and they also kill virally infected cells and malignant cells. NK cells are unique among the cells of the immune system in that they have the ability to recognize foreign, infected or stressed cells in the absence of antibodies and Major Histocompatibility Complex proteins (the cell surface proteins that act as bar codes used by the immune system uses to determine if a cell is yours or not yours). Therefore, NKs typically work faster than the rest of the immune system.

Natural killer cells or NK cells have been used to treat patients with refractory cancers. Unfortunately, a major problem with using NK cells is growing a sufficient quantity of cells for therapy. Using pluripotent stem cells to make NK cells is an intriguing possibility, but the protocols for differentiating NK cells from embryonic stem cells (ESCs) is tedious and inefficient. However, the Kaufman laboratory has provided a much more efficient and straight-forward way to derive NK cells, thus allowing for the production of clinical scale quantities of NK cells.

The Kaufman lab protocol involves first deriving embryoid bodies from ESCs or induced pluripotent stem cells (iPSCs), which are made from adult cells through genetic engineering techniques that causes the cells to de-differentiate into ESC-like cells known as iPSCs. Embryoid bodies are three-dimensional aggregates of pluripotent stem cells that assume a kind of spherical shape and have a variety of cells differentiating into a wide range of cell types. Embryoid bodies can contain beating heart muscle, neural-type cells, blood progenitors cells, and even muscle or bone cells in their interiors in a haphazard arrangement. Forming embryoid bodies or EBs from cultured ESCs or iPSCs is rather easy, but controlling the differentiation of the cells in the EBs is quite another matter.

embryoid bodies
embryoid bodies

Kaufman and others discovered that if the EBs were incubated with artificial antigen-presenting cells that expressed a surface-bound version of the protein IL21 (interleukin 21) plus a cocktail of cytokines, these pluripotent stem cells could efficiently form NK cells.

Functional assays of the NK cells differentiated from ESCs and iPSCs easily showed that the NK cells for functional in every way and expressed all the cell surface molecules characteristic of NK cells. Furthermore, all ESC and iPSC lines examined were able to make NK cells, but the efficiency with which they made them different rather widely.

In conclusion, Kaufman and others state in their paper, “our ability to now produce large numbers of cytotoxic NK cells means that prospect hESC- and iPSC-derived hematopoietic products for diverse clinical therapies can be realized in the not-too-distant future.” For some cancer patients, that day cannot come soon enough.

Published by

mburatov

Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).