How our 'killer' immune cells can be harnessed to beat diabetes and arthritis

Daily Mail​

14 hours ago

A 'game changing' new technique which wipes out rogue cells responsible for autoimmune conditions may offer the hope of a one-off treatment for many debilitating diseases.
Around four million people in the UK live with an autoimmune condition, according to a major study published in The Lancet.
These arise when immune cells produce faulty antibodies that mistakenly attack the body's own tissues, triggering inflammation and tissue damage. Depending on the condition, different parts of the body are affected.
In rheumatoid arthritis, for example, it's mainly the joints, with type 1 diabetes it is cells in the pancreas that produce insulin, and in multiple sclerosis, it's the nerves, leading to numbness and movement difficulties.
The new treatment harnesses the body's own immune defenders, 'natural killer' cells, to wipe out rogue white blood cells responsible for producing the antibodies that launch these attacks.
Early trials show it not only improves symptoms, but 'resets' the immune system, suggesting it may offer long-lasting relief.
Current treatment for autoimmune conditions often relies on long-term use of steroids and immunosuppressant drugs, but in reducing the immune response these can increase risk of infection, cancer and other complications.
In the absence of effective treatments many patients face years of fatigue, pain and disability.
More recently, scientists have begun trialling CAR-T therapy, better known as a cutting-edge cancer treatment, for autoimmune diseases such as lupus – where multiple tissues and organs come under attack, including the kidneys, lungs, joints and brain.
CAR-T therapy works by modifying a type of white blood cell called T cells so they recognise a marker on the cancer cell and then kill it.
While promising, 'one drawback to this approach is there can be significant side-effects', says Professor Lucy Walker, chair in immune regulation at the Institute of Immunity & Transplantation, University College London.
These include cytokine release syndrome, where the immune system goes into dangerous over-drive, triggering widespread inflammation, and neurological complications.
'While these may be acceptable in cancer settings, as late-stage cancer patients tend to be older, for autoimmune diseases, approaches with fewer side-effects are needed because they're chronic but not immediately life-threatening and often affect younger people,' she adds.
It's hoped the latest breakthrough (called CAR NK –which stands for Chimeric Antigen Receptor Natural Killer cells) may prove an even better option.
The CAR NK cells are a type of immune cell genetically engineered in the lab to target the cells that produce the faulty antibodies. The immune system then regenerates with 'normal' cells.
The difference with CAR-T therapy, says Professor Walker, is that with the newer technique the 'CAR' (an artificial protein that helps immune cells attack specific targets) is put in 'another type of white blood cell, the NK cell, in order to deliver the same killing effect, but with fewer toxicities'.
And while CAR-T cells must be made from the patient's own immune cells in a complex and time-consuming process, CAR NK cells can be manufactured in bulk from donor umbilical cord blood or stem cells, then frozen and stored ready for use, significantly reducing cost.
The treatment is already being tested on patients with lupus, a condition affecting around 70,000 people in the UK and which can be debilitating, even life-threatening.
After 27 people with severe lupus received an infusion of CAR NK cell therapy, all showed signs of improvement and 70 per cent went into full remission, according to results presented in June at a major rheumatology conference in Barcelona. What's more, there were no reports of serious side-effects.
In another study, published in Cell in June, researchers treated a patient with systemic sclerosis, a rare and serious autoimmune disease that attacks blood vessels and connective tissue, leading to organ damage.
After treatment, the patient's skin and blood vessels began returning to normal.
One benefit of using natural killer cells is they do not usually trigger rejection, so there is no need for a tissue match.
Professor Zhao Dongbao, a senior immunotherapy researcher at Shanghai's Naval Medical University and one of the lead investigators on the lupus study, told Good Health CAR NK therapy 'is expected to be used for the treatment of more than ten million patients worldwide, with more than one million patients with autoimmune diseases in the US and the UK'.
He says plans are under way for formal clinical trials for lupus, 'with potential expansion to other autoimmune diseases in the future'.
He believes the approach could 'transform care' for people with a wide range of autoimmune conditions.
But Professor Walker cautions: 'The approach is promising but is in its infancy – it's only been tested on a very small number of people.'
However, she says, if follow-up work 'showed it was successful, it could represent a much more targeted approach than long-term immunosuppression and potentially be tolerated much better'.
Luke Evnin, chair of the US-based Scleroderma Research Foundation, is upbeat: 'The promise is that in a single course of treatment, the patient would get lasting benefit and potentially stop other medicines and be freed from disease progression. It would be a game-changer.'