Our immune system is like the police force of our body, generally protecting us from harm such as infection or cancer, explains Johns Hopkins rheumatologist Maximilian F. Konig. When we encounter autoimmune diseases, it’s due to a few “bad cops” going rogue and attacking the normal citizens.

“We are working to develop precision therapies that will leave the ‘good cops’ unharmed, allowing patients to escape the potentially life-threatening complications that are so common with current therapies for autoimmune disease,” says Konig, whose lab (koniglab.edu) is based in the Ludwig Center, part of the Johns Hopkins Kimmel Cancer Center.

Konig is capitalizing on cellular therapy approaches that have become a standard of care in treating cancer to now develop the first precision treatments for devastating autoimmune diseases like lupus, rheumatoid arthritis and antiphospholipid syndrome, which is implicated in heart disease, stroke and pregnancy loss.

He feels a sense of urgency, since existing treatments for autoimmune diseases carry potentially toxic side effects that can be debilitating and even deadly. As rheumatologists, “we currently have to shut down the entire police force to get control of a very small population of ‘bad cops,’” he explains. The impact on patients? A high risk of infection, poor response to vaccines and treatment-related deaths.

Konig is building on advances in gene engineering and CAR-T cell therapy, a type of immunotherapy that is increasingly being used to treat patients with B cell-driven blood cancers, including lymphoma, leukemia and multiple myeloma. The treatment involves collecting a patient’s “killer” T cells, then reengineering those cells to recognize and attack the cancer by binding to proteins, or antigens, on the cancer cells’ surface. Different types of cancer have different antigens, so each type of CAR-T cell therapy is made to fight a specific kind of cancer antigen. After being reengineered, the cells are allowed to multiply and then infused back into the patient to do their cancer-fighting work.

“If we have such a unique and incredibly powerful tool to cure B cell cancers, could it be applied to treat B cell-driven autoimmune diseases?” asks Konig. He and others believe the answer is “yes.”

In his lab, Konig and his colleagues are developing and using a new generation of T cell therapy approaches — such as CRISPR-based engineering of chimeric autoantigen-T cell receptors (CATCR) — to reprogram a patient’s T cells so they can selectively eliminate self-reactive immune cells while safeguarding normal immune populations.

“These precision therapies have the potential to transform the lives of patients living with autoimmune and rheumatic diseases by providing new tailored treatments that can control autoimmunity without increasing the risk of infection that is common to all existing treatments,” says Konig.

Story by Sue De Pasquale and posted in the Hopkins Medicine Winter 2024 Magazine.