ddn Cancer Research News Exclusive: Natural-born killers
DURHAM, N.C.—A team of scientists from the University of Minnesota, the Integrated Center of Cellular Therapy and Regenerative Medicine of St. Anne's University Hospital Brno (Czech Republic) and the University of Texas, Houston, have published a new study on a method for mass-producing NK cells in the lab in quantities that could take NK cells-based therapies out of the lab and into the clinic.
Labs have been producing NK cells from human embryonic stem cells and induced pluripotent stem cells for some time, but up until this point it has only been possible on a small scale. This new method ramps up the output while streamlining the process to require less time and work.
"Human NK cells have been used to treat patients with refractory malignancies, but a major hindrance to expanded use has been the inefficiency of production," Anthony Atala, M.D., editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine, said in a press release. "The current study has identified a two-stage culture system to efficiently produce the cells in a manner more suitable to clinical translation than previous methods."
NK cells are a type of white blood cell known as lymphocytes. In a 2008 article that appeared in Nature Immunology ("Functions of natural killer cells), NK cells are described as "effector lymphocytes of the innate immune system that control several types of tumors and microbial infections by limiting their spread and subsequent tissue damage. Recent research highlights the fact that NK cells are also regulatory cells engaged in reciprocal interactions with dendritic cells, macrophages, T cells and endothelial cells. NK cells can thus limit or exacerbate immune responses. Although NK cells might appear to be redundant in several conditions of immune challenge in humans, NK cell manipulation seems to hold promise in efforts to improve hematopoietic and solid organ transplantation, promote antitumor immunotherapy and control inflammatory and autoimmune disorders."
Dan Kaufman, M.D., Ph.D., of the Stem Cell Institute of the University of Minnesota, notes that NK cells comprise roughly "10 percent of the lymphocytes in your blood," and demonstrate both antiviral and antitumor activity. Kaufman was the lead investigator for the study.
The study covers a "revamp" of their previous approach in producing these cells in greater quantities, Kaufman says. The original study, "Human embryonic stem cell-derived NK cells acquire functional receptors and cytolytic activity," appeared in the Journal of Immunology in 2005. In this latest study, "Clinical-scale derivation of natural killer cells from human pluripotent stem cells for cancer therapy," Kaufman says they got rid of xenogeneic and stromal cell lines, which are typically mouse lines, and are now able to mass-produce these cells "without any foreign cells or foreign serum," which allows them to generate these cells in "completely defined conditions that eliminate some of the possible barriers to clinical use because of FDA issues." The team was also able to adjust their culture processes to scale up the number of cells to reach levels sufficient for treating patients.
"Part of this is based just on the change of culture conditions we did, and then part was too the collaboration with the group at MD Anderson who provided what are called artificial antigen-presenting cells, and these were shown to give several lots more expansion of these NK cells that we can then use," Kaufman explains.
NK cells seem to be most effective when targeting leukemias or "liquid tumors," which Kaufman posits may be due to certain receptors that make the tumors more susceptible to NK cells. Other tests have been done with melanoma and some types of kidney cancers, which he notes "tend to be more immune-susceptible." Moving forward, he says, the team will be trying to use embryonic stem cells and induced pluripotent stem cells to determine whether it's possible to enhance the receptors and other facets that would lead to increased termination of tumors that generally present with less sensitivity.
Kaufman says they are reaching out to various outfits to see if they can find support for scaling this approach up and "either through academic or commercialization, provide a product that we could put into clinical trials." The NK cells have been shown in other studies to "have activity against things like pancreatic cancer, lung cancer, colon cancer, breast cancer," he adds.
Should they find that support, he says the most likely form that this approach will take will be to pair the NK cells with nanoparticles to deliver them to the tumors, or to engineer the NK cells with specific receptors.
"We think that this type of approach combined with chemotherapy—the chemotherapy might kill off most of the tumor, but the NK cells, the targeted NK cells, would then be able to kill off and mop up any residual tumor cells," Kaufman explains.
The most recent study appeared in STEM CELLS Translational Medicine March 20.