Anticancer Immunity Initiated with NK-cells: A Case Study of Bachanova and Memory-Like NK Cells

“The number of NK companies has just exploded,” says Todd Fehniger, an oncologist at Washington University School of Medicine in St. Louis, Missouri. The field is anxious to see which approach will give people long-lived results when researchers test their ideas in early trials. “We’re still at this inflection point in the field where we need that one clinical success, that one regulatory approval that will spark this torrent of interest,” Fehniger says.

Others are taking advantage of known activating and inhibitory receptors to bolster existing NK cells. Innate Pharma, a biotechnology firm based in Marseille, France, is testing an NK-cell checkpoint inhibitor in a phase III trial as a complement to T-cell checkpoint-inhibitor therapy for non-small-cell lung cancer. The drug blocks an inhibitory receptor found on NK cells and some T cells called NKG2A, unleashing both branches of the immune response.

The engagers from Innate were designed to bind tumour antigens to immune cells to increase their activity and bring them into close proximity to their targets. Engagers that bind T-cell receptors are already in clinical use, but they carry a high risk of cytokine release syndrome. NK-cell engagers pose a safer alternative that could still ignite anti-cancer immunity. The company’s tri-specific engager binds to blood-cancer proteins, CD16 and another NK-activating receptor; its tetra-specific engager has an added region that stimulates the IL-2 receptor on NK cells, but not on Treg cells. immunotherapy has been difficult due to the fact that the tetra-specific engager caused the NK cells to infiltrate lung tumours in mouse studies.

For Bachanova, the work and the wait are well worth it on the basis of the remissions she has seen over the years that avoid the intense side effects common with T-cell therapies. “The patients feel good,” she says. You can witness that. and it is powerful.”

They are testing a new therapy called memory-like NK Cells as an add-on therapy for patients with Acute Myeloid Leukemia. In experiments in which the NK cells came from the same donor, the cells multiplied 1,000-fold and lasted for at least 2 months9. His team is also detailing the characteristics that distinguish memory-like NK cells using tools such as mass cytometry, which can measure dozens of proteins or genes in millions of individual cells at a time. Fehniger co-founded the St Louis-based immunology company, Wugen, in which he obtained the licence for the NK cell protocol. Wugen is testing its own product in people with Acute Myeloid Leukemia and other tumors.

The study showed important variables about the cell source. People that experienced the best outcomes received cells grown from cord blood that were frozen within 24 hours of collection and lacked nucleated red blood cells, an indicator of physical stress. The one-year survival rate for those who received NK cells from optimal cord-blood units was over 70%. 5% of the cord blood did not meet the standards. The minute we came up with this, we changed our protocols to use the most optimal cord blood.

Two- to-four week wait for the cells that will be engineered is required for CAR-T therapy. When a cell’s cells are injected into another person, some of them develop a syndrome called cytokine release syndrome in which a rush of inflammatory molecule causes a variety of symptoms including low blood pressure, infections and hospitalization. About one-quarter can have life-threatening consequences. All of this makes the price of therapy high — around US$400,000 — and limits it to people who are able to withstand the side effects.

As part of a study published in January, 37 people who had been through various failed treatments for blood cancer received infusions of genetically enhanced immune cells that researchers hoped would clear their disease1. The concept was not new — therapies based on T cells have been approved since 2017. The source of the cells wasn’t clear.

Cancer kills almost ten million people annually. According to one study, this disease, in all of its many forms, will cost the world 25 trillion international dollars over the next 30 years. There was a report from the journal JAMA Oncol 9, 465–472. More than 50 years ago, the US launched a war on cancer and many people hoped that the disease would be defeated. There are a number of side effects and uncertain outcomes associated with treatment for cancer today. New treatments for cancer are needed to turn the tide decisively — and they are rapidly arriving.

Theranostics combines medical tasks with therapy and diagnostics in order to achieve better results. The idea is to send radioactive particles into the body to identify and locate cancer, and then follow up with a different class of emitters that can deal the cancer cells a death blow. Researchers are also exploring the use of artificial intelligence to help work out which therapy is best for an individual. The clinical trial system may be rethinking due to the rapid emergence of new treatments, which could cause people to be deprived of the most effective treatments.

We are pleased to acknowledge grant funding from MSD and the financial support of Pfizer in producing this Outlook. As always, Nature retains sole responsibility for all editorial content.