In a first-of-its-kind clinical trial, a natural killer cell immunotherapy derived from induced pluripotent stem cells is being tested for safety in 64 patients with a variety of solid tumors. The first patients received the cells in February at the University of California, San Diego (UCSD) Moores Cancer Center and MD Anderson Cancer Center.
“This is a landmark accomplishment for the field of stem cell–based medicine and cancer immunotherapy. This clinical trial represents the first use of cells produced from human induced pluripotent stem cells to better treat and fight cancer,” says Dan Kaufman of UCSD in a press release. Kaufman collaborates with Fate Therapeutics, a biotech firm that developed the therapy, and researchers at the University of Minnesota to develop natural killer (NK) cell products including the one...
NK cells are immune cells in the same family as T and B cells, and are very good at targeting cancer cells for destruction. Laboratory experiments have shown they do so by attacking cells that have lost their major histocompatibility complexes—self-recognition signals that tell the immune system not to attack—a phenomenon that can happen among cancer cells but not to healthy cells. Experts are not sure what proportion of cancer cells lose that signal, says Sandip Patel, who is the lead physician running the clinical trial at the Moores Cancer Center, but they are hopeful that the clinical trial can help determine which cancer patients could benefit the most from NK cell treatment.
To kill off cancer, the NK cells secrete cytokines and chemokines. Cancer patients may not be able to produce enough NK cells to fight their cancer, so the idea, says Patel, is to reinforce their supplies.
This clinical trial is targeting late-stage cancer patients with solid tumors, including lymphoma, colorectal cancer, and breast cancer. The so-called FT500 NK cells do not undergo any further alterations after their derivation from the induced pluripotent stem cells (iPSCs), offering the possibility of a quicker, ready-made treatment.
There are several other clinical trials using NK cells as an immunotherapy for cancer, but those trials use NK cells directly from a donor or from the patient. For instance, a clinical trial of NK cells in France is using NK cells on nine patients with gastrointestinal cancer, according to clinicaltrials.gov. Those NK cells were taken from donors and administered to the patient.
Approved cell therapies for cancer also rely on modifying T cells, in those cases to produce cancer cell–binding chimeric antigen receptors (CARs), and have been effective in treating certain cancers such as leukemia, Patel tells The Scientist. Those approaches have had limited success against solid tumors, but NK cells have the potential to be a better treatment option if those cancer cells have lost MHC.
See “The Next Frontier of CAR T-Cell Therapy: Solid Tumors”
The main disadvantage of taking cells from a patient and developing them into a cellular immunotherapy product is that the process can take weeks. “But for the majority of patients who may not be a candidate or may not have time to wait for such an approach, the idea that there’s an off-the-shelf immunotherapy that could potentially as a living drug act against their cancer, I think is a really exciting concept,” Patel tells The Scientist.
The NK cells can evade immune rejection even if they are derived from donor iPSCs because they do not produce the human leukocyte antigens on their cell surfaces that activate the body’s immune cells. Because FT500 is a cell product that can be used by anyone, “it’s immediately accessible to the patient without having to wait for [the] few weeks that’s required to make the cell product,” says Uma Lakshmipathy of Thermo Fisher Scientific who is not involved with the trial. Lakshmipathy is the director of research and development where she uses her expertise in stem cell research to guide the development of analytical assays and other workflow advancements, especially for CAR T therapies.
However, iPSCs are difficult to work with. “They’re really challenging because they spontaneously differentiate,” says Teisha Rowland of the University of Colorado Boulder who is not involved with the trial. Rowland is the director of the Stem Cell Research and Technology Resource Center and has worked extensively with iPSCs. She says that researchers must visually inspect them daily and physically remove cells that are showing signs of differentiation. iPSCs require very clean conditions without antibiotics because those can affect the differentiation abilities of the cells, according to Rowland. This could present a challenge to scaling up the production of iPSC-derived NK cells to use as a cell therapy.
Although this clinical trial is in the beginning stages with an expected end date of June 2020, experts are optimistic that this iPSC-derived NK cell approach will generate promising and effective treatments. “We are closer than we think,” says Lakshmipathy.
Correction (May 8): The original version of this article erroneously stated that a clinical trial used NK cells as a cell therapy for neuroblastoma. It used NK T cells. This example has been removed and replaced with an example of a clinical trial using NK cells. The Scientist regrets the error.