A Novel Therapy for Autoimmune Diseases
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The more I explore the extraordinary intelligence that is our immune system and its intimate relationships with other body systems (say, our autonomic nervous system, enteric nervous system or belly brain, and pain perception system), the more my imagination wanders.
I wonder, for instance, if some forms of cancer—say, pancreatic cancer—might turn out to be viruses that learn to attack healthy body processes?
Wonderings aside, researchers have long viewed autoimmune disease and cancer as two sides of the same coin. An immune response against self-antigens results in autoimmune disease. In contrast, a lack of response to malignant cells allows cancer to develop.
Studying autoimmune diseases, researchers believe, can lead to breakthroughs in the development of drugs that treat cancer.
Today I’d like to report on a new discovery that has electrified the field of oncology: chimeric antigen receptor T-cell (CAR-T) therapy.
You can think of this therapy as “engineered” immune cells. The CAR-T technique involves “redesigning” a person’s T cells (an immune system cell) to carry a receptor that directs the cells to attack tumors.
In 2017, the U.S. Food and Drug Administration (FDA) approved two CAR-T products that treat cancers of the blood or blood tissues.
In an interview with Anthony King for the prestigious journal Nature, Dr. Martin Pule called the therapy “the most important therapeutic innovation in hematology in a generation.”
In 2022, synthetic biologist Wendell Lim at the University of California, San Francisco and a group of colleagues successfully programmed CAR-T cells to produce interleukin-2 (IL-2), an inflammatory cytokine, only when the engineered cell encountered a cancer cell.
Remarkably, the IL-2 production proved to be most effective at fighting pancreatic cancer tumors in mice when activate via a pathway separate from the one the mouse immune system uses to recognize the cancer cell. This new insight, scientists say, could help in shaping future treatments for pancreatic cancer. (At present, pancreatic cancer has one of the poorest prognoses of all forms of cancer.)
At present, the therapy is challenging to produce, taking as long as three weeks to create—a delay that proves to be deadly for patients who die, or who become too sick to treat, before it is ready to administer.
And it just so happens that the new therapy has had a startling impact on autoimmune disease.
A December, 2023 feature, also in Nature, chronicles the results of an extraordinary study presented on December 9, 2023 at the American Society of Hematology’s Annual Meeting in San Diego, California.
I love the collaborative and integrative way this breakthrough came about. (In fact, this kind of interdisciplinary dialogue, collaboration, and inquiry has been the impetus for my own integrative work.)
In 2019, researchers demonstrated that CAR-T cells capable of recognizing B cells were able to reduce symptoms of a disease in mice that resembled lupus, an autoimmune disorder that affects several organ systems.
Several oncologists from University Hospital in Erlangen, Germany were establishing their own CAR-T Center to provide cancer treatment.
A rheumatologist who attended a meeting hosted by the Center asked the cancer specialist for advice on treating a women with lupus (systematic lupus erythematosus, a severe autoimmune disease). Several of the woman’s organs had begun to fail. She did not have long to live, and insisted her doctors try something else.
The team thought of the 2019 study of a lupus-like disease in mice. However, they hesitated to try it in humans. For one thing, the therapy can induce severe side effects. For another, prior to the treatment, recipients must first receive intensive chemotherapy to destroy many of their existing immune cells.
Fabian Muller, one of the presenters at the San Diego conference and an oncologist at Friedrich-Alexander University of Erlangen-Nuremburg in Germany, told Nature that his team was frightened to try the treatment, especially on a patient so ill.
The courageous woman insisted that they attempt it.
Remarkably, she experienced minimal adverse side effects.
Several other patients followed, also with minimal side effects.
The Erlangen team used the method to treat two additional autoimmune disorders: systemic sclerosis and idiopathic inflammatory myositis.
The successes piled up, one on top of another.
In December of 2023, another team in Germany added a fourth autoimmune disease, myasthenia gravis, to the list of successes.
What’s more, all fifteen patients have remained virtually symptom free since their treatment—a period of two years.
Marcela Maus, who designs CAR-T therapies at Massachusetts General Hospital in Boston, observed that this was only the beginning. “There is so much that can be done that was unthinkable a decade ago,” she told science writer Heidi Ledford of Nature.
Sources:
Wonderings aside, researchers have long viewed autoimmune disease and cancer: Sakowska, J., Arcimowicz, Ł., Jankowiak, M., Papak, I., Markiewicz, A., Dziubek, K., Kurkowiak, M., Kote, S., Kaźmierczak-Siedlecka, K., Połom, K., Marek-Trzonkowska, N., & Trzonkowski, P. (2022). Autoimmunity and Cancer-Two Sides of the Same Coin. Frontiers in immunology, 13, 793234. https://doi.org/10.3389/fimmu.2022.793234
The CAR-T technique involves “redesigning” a person’s T cells: King, A. (2020). Building better CAR-T therapies. Nature, 585(7826), S4–S6. https://doi.org/10.1038/d41586-020-02675-w
In an interview for a different article in Nature, Dr. Martin Pule: King, A. (2020). Building better CAR-T therapies. Nature, 585(7826), S4–S6. https://doi.org/10.1038/d41586-020-02675-w
In 2022, synthetic biologist Wendell Lim at the University of California, San Francisco and a group of colleagues successfully programmed CAR-T cells: Ledford, H. (2022). Cancer treatments boosted by immune-cell hacking. Nature. https://doi.org/10.1038/d41586-022-04465-y
Remarkably, the IL-2 production proved to be most effective at fighting pancreatic cancer tumors in mice: Ledford, H. (2022). Cancer treatments boosted by immune-cell hacking. Nature. https://doi.org/10.1038/d41586-022-04465-y
A December, 2023 feature, also in Nature, chronicles the results of an extraordinary study: Ledford, H. (2023). ‘It’s all gone’: CAR-T therapy forces autoimmune diseases into remission. Nature, 624(7992), 483–484. https://doi.org/10.1038/d41586-023-03968-6
In 2019, researchers demonstrated that CAR-T cells capable of recognizing B cells were able to reduce symptoms: Kansal, R., Richardson, N., Neeli, I., Khawaja, S., Chamberlain, D., Ghani, M., Ghani, Q. U., Balazs, L., Beranova-Giorgianni, S., Giorgianni, F., Kochenderfer, J. N., Marion, T., Albritton, L. M., & Radic, M. (2019). Sustained B cell depletion by CD19-targeted CAR T cells is a highly effective treatment for murine lupus. Science translational medicine, 11(482), eaav1648. https://doi.org/10.1126/scitranslmed.aav1648
A rheumatologist who attended a meeting hosted by the Center asked the cancer specialist for advice: Ledford, H. (2023). ‘It’s all gone’: CAR-T therapy forces autoimmune diseases into remission. Nature, 624(7992), 483–484.
Fabian Muller, one of the presenters at the San Diego conference and an oncologist: Mueller, F. (2023, December 9). CD19-Targeted CAR-T Cells in Refractory Systemic Autoimmune Diseases: A Monocentric Experience from the First Fifteen Patients. 65th ASH Annual Meeting & Exposition. https://ash.confex.com/ash/2023/webprogram/Paper180547.html
In December of 2023, another team in Germany added a fourth autoimmune disease, myasthenia gravis: Haghikia, A., Hegelmaier, T., Wolleschak, D., Böttcher, M., Desel, C., Borie, D., Motte, J., Schett, G., Schroers, R., Gold, R., & Mougiakakos, D. (2023). Anti-CD19 CAR T cells for refractory myasthenia gravis. The Lancet. Neurology, 22(12), 1104–1105. https://doi.org/10.1016/S1474-4422(23)00375-7