Health
Synthetic IL-9 receptors allow T cells to fight cancer without the need for chemotherapy or radiation
Before a patient receives T-cell therapy designed to target cancerous tumors, the patient’s entire immune system must be destroyed with chemotherapy or radiation. Toxic side effects such as nausea, extreme fatigue and hair loss are well known.
Currently, a research team led by Anusha Kalbasi, MD at UCLA, working with scientists from Stanford University and the University of Pennsylvania, has shown that synthetic IL-9 receptors enable the fight against these cancers. T cells Work without the need for chemotherapy or radiation. T cells engineered with synthetic IL-9 receptors designed in Dr. Christopher Garcia’s laboratory at Stanford University were potent against mouse tumors, as announced Wednesday. Nature..
When T cells signal through synthetic IL-9 receptors, T cells not only defeat the existing immune system, but also acquire new functions that help kill cancer cells more efficiently. increase. I currently have patients suffering from toxic chemotherapy just to wipe out the existing immune system so that T cell therapy has a chance to fight. However, with this technique, T-cell therapy can be given without pre-cleaning the immune system. “
Anusha Kalbasi, MD, UCLA
Karbasi, a researcher at the UCLA Jonsson Comprehensive Cancer Center and an assistant professor of radiation oncology at UCLA’s David Geffen School of Medicine, begins work under the guidance of senior research researchers Antoni Ribas, MD, and PhD. Did. The study was also led by Dr. Mikko Siurala, MD, Carl June, MD, University of Pennsylvania, and Dr. Leon L. Su, Garcia Lab, Stanford University.
“This discovery opens the door to being able to give T cells in the same way as blood transfusions,” Rivas said.
Ribas and Garcia focus on the notion that synthetic versions of the key T cell proliferation cytokine, interleukin-2 (IL-2), can be used to stimulate T cells engineered on the corresponding synthetic receptors. We cooperated in a paper published in 2018. Synthetic IL-2. This system allows T cells to be manipulated by treating the patient with synthetic cytokines (which do not affect other cells in the body) even after the T cells have been administered to the patient. Intrigued by the study, Karbasi et al. Interested in testing modified versions of synthetic receptors that transmit other cytokine signals from the common gamma chain family, IL-4, -7, -9, -21. I had it.
“Among the synthetic common gamma chain signals, it was clear early on that the IL-9 signal was worth investigating,” Kalbasi said, and unlike other common gamma chain cytokines, IL-9 signaling. Added that it is usually inactive in nature. T cells that develop. Synthetic IL-9 signals have made T cells uniquely combined with both stem cell and killer-like properties, making them more robust in the fight against tumors. “In one of our cancer models, we cured more than half of the mice treated with synthetic IL-9 receptor T cells.”
According to Kalpasi, this treatment has proven effective in multiple systems.They have two cancer models that are difficult to treat in mice (pancreatic cancer and pancreatic cancer). melanoma – And used T cells that target cancer cells via natural T cell receptors or chimeras antigen Receptor (CAR). “This treatment worked whether the cytokine was administered to the whole mouse or directly to the tumor. In all cases, T cells engineered with synthetic IL-9 receptor signaling are superior. Helped to treat if some tumors in the mouse could not be treated. Otherwise. “
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Journal reference:
Kalpasi, A. , et al. (2022) Enhancement of adoptive cell therapy using synthetic IL-9 receptors. Nature.. doi.org/10.1038/s41586-022-04801-2..
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