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AAIC 2023 | Phase I trial of NK cell therapy in advanced Alzheimer’s disease
Natural Killer (NK) cells have critical protective and regulatory roles in the central nervous system. Preclinical studies have shown NK cells to slow amyloid progression and eliminate autoreactive T-cells and damaged neurons. Paul Y Song, MD, NKGen Biotech, Santa Ana, CA, introduces SNK01, a first-in-kind, autologous, non-genetically modified NK cell product, created to take advantage of the NK cells’ role in the body. NK cells are harvested from the patient’s blood, activated and modified for enhanced cytotoxicity and increased activating receptor expression, and expanded to produce millions of cells. In a Phase I dose escalation study in 9 patients with advanced Alzheimer’s disease, NK cells were successfully collected, activated, and expanded from every patient, and were able to cross the blood-brain barrier. Reductions in cerebrospinal fluid biomarkers were also noted, including amyloid, p-tau, and neuroinflammatory markers. Dr Song comments on the potential advantages of such an approach and future plans to begin a Phase II international trial. This interview took place at the Alzheimer’s Association International Conference® (AAIC) 2023 in Amsterdam, Netherlands.
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Transcript (edited for clarity)
So one of the things that I don’t think people really appreciate is how NK cells play a real overall regulatory role and protective role in human health and specifically with regard to neurological diseases. They can influence the amount of protein accumulation in the brain, but they can also help really regulate the amount of inflammation that occurs in the brain. So what we’re able to do is take natural killer cells from individual patients...
So one of the things that I don’t think people really appreciate is how NK cells play a real overall regulatory role and protective role in human health and specifically with regard to neurological diseases. They can influence the amount of protein accumulation in the brain, but they can also help really regulate the amount of inflammation that occurs in the brain. So what we’re able to do is take natural killer cells from individual patients. We can get them to grow into massive quantities, but greatly enhance and activate them without any genetic modification. What we mean by that is we make them inherently stronger, higher cytotoxicity, but also because of the activating receptor expression, they’re much more in tune to identify things in your body that shouldn’t be there.
So in our trial, when we took natural killer cells from patients with a pretty advanced Alzheimer’s, the median score of the MMSE was 14. So if you look at a lot of the trials that are being presented here, it’s mostly dealing with therapeutics for mild cognitive impairment. We took patients much more advanced. We’re able to take their natural killer cells, highly activate and expand them and then give them back to patients through the IV. Once they were given IV, they were able to cross the blood-brain barrier to do three things. We measured cerebrospinal fluid levels of protein as well as inflammation, and we found that we were able to reduce both amyloid and p-tau proteins as well as several neuroinflammatory markers.
So up to now we’ve done four clinical trials in cancer, and we’ve just completed our Phase I in Alzheimer’s disease and we have not had any dose limiting toxicity, any drug related adverse event. So it’s very, very safe and we do think that this is something that lends itself to being able to be repeatedly dosed without any side effects. There’s no pre-treatment, there’s no need to do any lymphodepletion measures and most of our patients have found the overall process to be really very, very simple.
So we wanted to really show proof of concept with the Phase I. one that our natural killer cells could indeed cross the blood brain barrier, meaning that when you gave it peripherally in an IV, it got into the brain to reduce inflammation and as well as proteins and have some effect on cognitive improvement and now our goal is to move forward with a Phase II international trial.