Treatment offers new hope for lupus, and possibly other autoimmune diseases too


When real patients see unprecedented positive results with a new treatment, it’s tempting to call it a “breakthrough” for medical science. This describes the excitement over a new report from German researchers on a radical new treatment for lupus.

The patients in the study – five people with severe lupus – went into remission after pioneering treatment with CAR T-cell, which uses genetically modified cells.

So what is lupus, why is it such big news, and what could it mean for other patients and diseases?

Lupus and the immune system

Around 5 million people are affected by some form of lupus worldwide. The most common form of lupus is technically known as systemic lupus erythematosus. Although not widespread, it is more common than multiple sclerosis (MS). Both are “autoimmune” diseases where the immune system attacks its owner instead of the germs it is supposed to fight.

MS is an autoimmune disease in which the immune system attacks nerve tissue. In contrast, lupus can affect any organ in the body. Treatments for lupus have been so poor for so long that even rich and famous people with the disease — like pop star and actress Selena Gomez — have had organ failure requiring kidney transplants. Many complicating factors have made it difficult to improve outcomes for people with the disease.

First, the variety of tissues that lupus can affect means that no two patients are the same. Diagnosis is difficult and often late. It also means that we researchers have to deal with great complexity when trying to determine what causes the disease.

This clinical variability makes it difficult to measure improvement in treatment response, and many clinical trials have likely failed due to measurement issues.

Second, there are variations between patients in which part of the immune system goes wrong. This means that different patients will need different treatments – and we still don’t know for sure how to get it right.

But progress is moving fast.

Innate and adaptive immunity

The immune system is in two parts.

The “innate” immune system responds quickly but non-specifically to viruses and other germs that hit the body with a mass of germ-killing inflammatory proteins. The “adaptive” immune system is slower but more precise. It kicks in after the innate immune system and provides long lasting defense against the invading germ.

When you’re vaccinated against a disease (like COVID), the fever and body aches you might have on the first day or two are your innate immune system at work. But long-lasting antibody protection is provided by a part of your adaptive immune system, a key part of which is delivered by cells called “B cells.”

In lupus, both parts of the immune system are involved and both have been used successfully to develop drugs. Earlier this year, the Therapeutic Goods Administration approved anifrolumab, a drug that blocks “interferon,” a crucial protein made by the innate immune system.

Another drug that acts on the B cells of the adaptive immune system, called belimumab, was approved a few years ago. Unfortunately, neither drug is on the Pharmaceutical Benefits Scheme yet, so access is extremely limited.

However, we now know that interferon and B cells are both important, and so very potent treatments that almost completely eradicate one or the other could be helpful. That’s where this potential new treatment comes in.

Already used to treat cancer

Treatments to destroy B cells are used in cancers like lymphoma. The most potent of these uses CAR-T cells, which are a type of cell naturally occurring to be a B-cell killer.

CAR-T drugs are very complex to manufacture and extremely expensive, but they work.

T cells are taken from the blood and then reworked in a special laboratory.

Now, this new report shows that targeting B cells using this approach could also be effective in lupus. Building on a very first patient treated in this way by the same group a year ago, doctors in Germany created a “homemade” CAR-T treatment and used it in five patients with severe lupus.

Remarkably, all five patients had almost complete eradication of the disease, allowing them to stop conventional medications, such as steroids, with potentially harmful side effects.

What this means for other patients

So what does this mean for patients in Australia? Well, most centers are unable to manufacture their own CAR-T treatments, so delivering this potential treatment will require a commercial approach.

However, it could be faster to market than other treatments in development because it takes a proven approach to a new disease, rather than being new from scratch.

One day, we may even be able to extend these treatments to other autoimmune diseases, such as multiple sclerosis, where B-cell treatments have been helpful, as well as lupus.

This should be weighed against the risk. It is important to note that the short-term side effects of CAR-T treatment (which include brain and bone marrow problems) can be serious. For this reason, such treatment would only be used for the most severe cases where standard treatments failed, such as the patients in the German trial.

Long-term side effects are also unknown at this time, and of course suppressing the immune system so profoundly as part of a pandemic is not without major risks.

Formal trials of a commercial CAR-T drug for lupus are already at an advanced stage of planning, and Australia is likely to be the focus of these trials due to our lupus expertise and environment. regulations conducive to testing. With all of these advances, we can finally tell our lupus patients, friends and family that there is light at the end of what has been a very long tunnel.

Eric Morand, Director, Monash Health School of Clinical Sciences, Monash University

This article is republished from The Conversation under a Creative Commons license. Read the original article.


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