The immune-system agents called natural killer cells (artificially coloured) can be bioengineered to attack cells that produce dangerous antibodies.Credit: National Institute of Allergy and Infectious Diseases/National Institutes of Health/Science Photo Library
Supercharged ‘natural killer’ cells could become a potent way to reset a disordered immune system — and thus quench some autoimmune disorders.
Results from two small clinical trials suggest that researchers can engineer natural killer cells — immune cells that destroy infected or diseased cells — to assassinate the renegade cells that produce antibodies against the body’s own tissues. These ‘autoantibodies’ can damage those tissues, fuelling autoimmune diseases such as lupus and systemic sclerosis.
“Natural killer cells have evolved to seek and destroy abnormal cells,” says Nadir Mahmood, president of Nkarta, a biotechnology company in South San Francisco, California. “And if that’s deep enough to drive an immune-system reset, then you can have the reconstitution of a healthy and naive immune system.”
Findings from one trial were announced in June at the European Alliance of Associations for Rheumatology (EULAR) meeting in Barcelona, Spain. Results from the other trial were published in the journal Cell1.
Before the killers
This approach has its roots in cancer therapies that rely on another kind of immune cell, called T cells, that can be genetically engineered to recognize and kill tumours. The engineered cells use a protein called a chimaeric antigen receptor (CAR) to identify their targets, and are therefore called CAR T cells.
CAR T cells can send some forms of blood cancer into remissions lasting more than a decade, and they have shown early promise against certain autoimmune disorders. But CAR-T-cell therapies on the market now are expensive and complicated to make: each treatment must be manufactured from the recipient’s own T cells.
‘It’s all gone’: CAR-T therapy forces autoimmune diseases into remission
These factors mean that, at present, only about one-quarter of people in the United States who might benefit from CAR-T-cell cancer therapies can access them, says Katy Rezvani, who studies cell therapy at the University of Texas MD Anderson Cancer Center in Houston. “There are five times as many patients with autoimmunity as there are with cancer,” she says. “So how are we ever going to be able to afford these expensive therapies for autoimmune disorders?”
Natural killer cells, however, can be taken from a blood donor and genetically modified to produce CAR NK cells, which can be frozen and used to treat multiple people. Rezvani says that her colleagues at MD Anderson can make hundreds of doses of CAR NK cells from a single donation of umbilical-cord blood.
Perfect fit?
The first trials of CAR NK cells have been in cancer and have had mixed early results, says Mahmood. One possible limitation is that these cells are shorter-lived than are CAR T cells, says Max Qian, chief executive of Rui Therapeutics, a company in Nanjing, China, that is developing CAR-NK-cell therapies. “If the tumour comes back, you need the drug to still be in the body,” he says.
But the cells’ fleeting presence might not be a problem for treating autoimmune diseases. A brief treatment with CAR NK cells could be enough to wipe out autoantibody production, Qian adds, or a person could receive several doses of the treatment if needed. After that, the immune system could rebuild itself with a fresh population of antibody-producing cells that have not been triggered to make autoantibodies.
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Late last year, Nkarta announced that it would end its efforts to make CAR-NK-cell cancer therapies and will instead focus on autoimmune disorders. “It seemed like CAR-NK-cell therapy was tailor-made for autoimmune disease,” says Mahmood.
