Dr. Maximilian F. Konig, an Assistant Professor of Medicine at the Johns Hopkins School of Medicine, is leading groundbreaking research to transform how we treat autoimmuneAny disorder in which loss of function or destruction of normal tissue arises from humoral or cellular immune responses to the body’s own tissue constituents.... diseases. Originally from Germany, Dr. Konig moved to the U.S. to train in rheumatology, and now he’s working to create new, precise drugs for autoimmuneAny disorder in which loss of function or destruction of normal tissue arises from humoral or cellular immune responses to the body’s own tissue constituents.... conditions.
During his rheumatology fellowship, Dr. Konig noticed two big challenges with current treatments:
- Many medications weren’t strong enough to keep patients well.
- Doctors had a hard time predicting which drugs would work for a given patient.
“When we prescribe immunosuppressive drugs for arthritisArthritis is the swelling and tenderness of one or more joints. Learn more. or autoimmuneAny disorder in which loss of function or destruction of normal tissue arises from humoral or cellular immune responses to the body’s own tissue constituents.... muscle inflammationInflammation is a normal part of the body’s defense to injury or infection, and, in this way, it is beneficial. But inflammation is damaging when..., it often feels like flipping a coin,” says Dr. Konig. “Sometimes the treatment works, but sometimes it doesn’t.”
He also saw that many patients experienced serious infections. This is because current drugs suppress the whole immune system, not just the parts causing harm.
This inspired Dr. Konig to explore disease-tailored treatment approaches. “If we could remove only the 1% of harmful immune cells [the ones that drive autoimmuneAny disorder in which loss of function or destruction of normal tissue arises from humoral or cellular immune responses to the body’s own tissue constituents.... disease] and keep the 99% of healthy cells that protect us from infections intact, we could have powerful treatments without any risk of infections,” he explains.
To do this, Dr. Konig and his team developed a new type of cell therapy called chimeric autoantigen-T cell receptor (CATCR)-T cells. This treatment targets only the specific immune cells causing a given autoimmune diseaseAny disorder in which loss of function or destruction of normal tissue arises from humoral or cellular immune responses to the body’s own tissue constituents.....
Here’s how the CATCR-T cell therapy works:
- The team collects T cells (a type of immune cell) from a patient or donor.
- In the lab, these cells are activated and multiplied.
- Using precise gene-editing technology (CRISPR), they remove the part of the T cells that usually recognizes threat (or cause autoimmune diseaseAny disorder in which loss of function or destruction of normal tissue arises from humoral or cellular immune responses to the body’s own tissue constituents.... if coming from the patient).
- This creates a “blank slate” T cell that can be reprogrammed.
- They then engineer these T cells with a new precision receptor (the CATCR, “catcher”) to recognize only the harmful B cells (another type of immune cell) causing the autoimmune diseaseAny disorder in which loss of function or destruction of normal tissue arises from humoral or cellular immune responses to the body’s own tissue constituents.....
- Finally, these living precision drugs are used to seek out and destroy only the harmful B cells, leaving the ones that are protective intact.
To test this new therapy, Dr. Konig’s team is focusing on antiphospholipid syndrome (APS) first. APS is an autoimmune diseaseAny disorder in which loss of function or destruction of normal tissue arises from humoral or cellular immune responses to the body’s own tissue constituents.... that causes blood clots and pregnancy losses, but therapies have not significantly improved over the past 30 years. In APS, the immune system mistakenly attacks certain proteins in the blood and on blood vessel walls.
“We understand quite well how APS works,” Dr. Konig says. “We know there are autoantibodies – proteins secreted from immune cells called B cells – that target self-proteins in the plasma and on endothelial cells. When they bind, they activate the immune system and clotting pathways that lead to inflammationInflammation is a normal part of the body’s defense to injury or infection, and, in this way, it is beneficial. But inflammation is damaging when..., thrombosis, or early pregnancy loss.”
By creating engineered T cells that can specifically recognize and eliminate only the B cells producing these harmful antibodiesAntibodies are proteins that protect you when an unwanted substance enters your body. Produced by your immune system, antibodies bind to these unwanted substances in..., Dr. Konig hopes to treat APS more effectively, in a predictable manner, and with fewer side effects than current treatments.
The patient impact of this precision therapy approach could offer several benefits for patients:
- Effective control of the disease
- Fewer side effects, as it doesn’t suppress the whole immune system
- Reduced risk of infections
- Longer periods without symptoms with potentially lasting disease control
Dr. Konig’s team has seen promising results in lab tests, and they hope to start clinical trials for patients with APS who haven’t responded to other treatments within the next few years. In parallel, they are moving forward to applying this and other precision therapies to other autoimmuneAny disorder in which loss of function or destruction of normal tissue arises from humoral or cellular immune responses to the body’s own tissue constituents.... and rheumatic diseases in which patients face similar treatment challenges.
This innovative approach is a major step forward in treating autoimmuneAny disorder in which loss of function or destruction of normal tissue arises from humoral or cellular immune responses to the body’s own tissue constituents.... diseases, offering hope for safer and more effective therapies that could improve the lives of many patients.
Maximilian F. Konig, MD, received the Foundation’s Investigator Award in 2023 – a three-year award. The InvestigatorIn research, a person who is involved in running a clinical trial or research study. The investigator may help prepare and carry out the protocol... Award encourages junior investigators to continue conducting innovative research while they establish themselves as independent investigators and secure larger-scale funding opportunities.