In a first-of-its-kind trial in the United States, researchers are testing a stem cell-derived natural killer cell immunotherapy in people with incurable cancer.

Cancer follows heart disease as the second biggest killer worldwide. In the United States, an estimated 606,880 people will die due to cancer in 2019. With the advent of immunotherapy, researchers hoped to boost a person's immune system to fight and destroy tumors effectively. Although this type of therapy has completely changed the treatment landscape for cancers such as melanoma, there remain a significant number of people whose tumors can evade their immune system.

Joining the likes of adoptive cell transfer and checkpoint inhibitors on the list of immunotherapies are natural killer (NK) cells. These specialized white blood cells come equipped with a potent armory of tools to make short work of cancer cells.

Now, researchers at the University of California (UC) San Diego School of Medicine are running a clinical trial with industrial collaborator Fate Therapeutics to investigate NK cells both alone and in combination with checkpoint inhibitors in people with advanced solid tumors.

One particular factor sets this study apart from others using NK cells for similar purposes. This "off-the-shelf" NK immunotherapy trial is the first in the United States to use cells that the researchers have derived from induced pluripotent stem (iPS) cells.

Using stem cells to kill cancer

Scientists first developed human iPS cells in 2006 by switching on four dormant genes in skin cells. Doing this completely changed the characteristics of these cells and reverted them to an embryonic-like state.

Now widely hailed as an alternative to embryonic stem cells, iPS cells can, like their embryonic counterparts, develop into any type of cell. For scientists who work on cell therapies, this provides a solution to a major stumbling block in advancing their technologies to clinical application.

Many therapies make use of a patient's own cells or cells from a donor. While this type of personalized treatment is the mainstay of current cell therapy applications, it is costly and time-consuming.

The use of iPS cells, on the other hand, allows researchers to produce a never-ending stream of cells. All that they need is a robust method to turn iPS cells into the particular cell type that they require.

A single iPS cell can thus become an "off-the-shelf" source of cells for therapy, which it is easy to produce time and time again.

Back in 2013, Dr. Dan Kaufman—professor of medicine in the Division of Regenerative Medicine and director of cell therapy at UC San Diego School of Medicine—and his team developed a method of expanding large numbers of NK cells from human iPS cells for cancer therapy. They published the method in the journal Stem Cells Translational Medicine.

After extensive preclinical testing, the US Food and Drug Administration (FDA) gave Dr. Kaufman and Fate Therapeutics the go-ahead last November to set up a phase 1 clinical trial to test their iPS-derived NK immunotherapy in people with advanced solid tumors.

First 'off-the-shelf' cancer immunotherapy

The phase 1 trial started in February and will include up to 64 people with advanced, untreatable cancer. The main aim of the trial is to assess the safety of the treatment. The other objectives are to determine the extent to which the tumors respond to NK cell therapy and to find out how long the cells stay in the participants' bodies.

The team will administer the cells once per week for 3 weeks, either on their own or in combination with one of three checkpoint inhibitors, namely nivolumab, pembrolizumab, or atezolizumab. The study is an open-label trial, which means that all of the study participants will know which treatment they are receiving.

"This is a landmark accomplishment for the field of stem cell-based medicine and cancer immunotherapy," explains Dr. Kaufman in a press release. "This clinical trial represents the first use of cells produced from human-induced pluripotent stem cells to better treat and fight cancer."

"Together with Fate Therapeutics, we've been able to show in preclinical research that this new strategy to produce pluripotent stem cell-derived natural killer cells can effectively kill cancer cells in cell culture and in mouse models," he continues.

The first person to receive treatment as part of the trial was Derek Ruff. After 10 years in remission, Mr. Ruff has stage IV colon cancer, which is progressing despite aggressive treatment.

"Coming to a [National Cancer Institute] cancer center means a lot to me. My options aren't otherwise good. Some people may not opt for a clinical trial, but for me, I want a chance at a cure."

—Derek Ruff

It will be a while before the results of the trial are available, with expectations being that the study will run into 2022. However, it paves the way not only for a new generation of immunotherapies to treat cancer but also for other iPS-derived cell therapies to follow. Watch this space.