a, Gating strategy for massive cytometry data to capture live CD8 + singlet T cells from an in vitro T cell culture for downstream analysis of phenotype and T cell function b, Gating strategy for massive cytometry data to capture living CD8 + singlet T cells infiltrating the tumor for downstream analysis of cell number, phenotype, and function T. Credit: Nature (2022). DOI: 10.1038 / s41586-022-04801-2
Before a patient can undergo T-cell therapy designed to attack cancerous tumors, the patient’s entire immune system with chemotherapy or radiation must be destroyed. Toxic side effects are well known, such as nausea, extreme fatigue, and hair loss.
Now, a research team led by Dr. Anusha Kalbasi of UCLA, in collaboration with scientists at Stanford and the University of Pennsylvania, has shown that a synthetic IL-9 receptor allows T cells to fight against cancer do their job without the need for chemotherapy. or radiation. T cells designed with the synthetic receptor IL-9, designed in the laboratory of Christopher Garcia, Ph.D., at Stanford, were potent against tumors in mice, as published Wednesday in Nature.
“When T cells are signaling through the synthetic IL-9 receptor, they get new functions that help them not only overcome the existing immune system, but also kill cancer cells more efficiently,” he said. Kalbasi. “Right now I have a patient who is struggling with toxic chemotherapy just to get rid of their existing immune system, so that T cell therapy may have a chance to fight. But with this technology you can give T cell therapy. without having to get rid of the immune system first. “
Kalbasi, a researcher at UCLA Jonsson Comprehensive Cancer Center and an adjunct professor of radiation oncology at UCLA’s David Geffen School of Medicine, began work under the tutelage of MD, Ph.D. Antoni Ribas, senior researcher of the study. The study was also led by Mikko Siurala, Ph.D., of Carl June Laboratory, MD, Penn, and Leon L. Su, Ph.D., of Garcia Lab, Stanford.
“This finding opens a door for us to donate T cells in the same way we do a blood transfusion,” Ribas said.
Ribas and Garcia collaborated in an article published in 2018 that focused on the concept that a synthetic version of interleukin-2 (IL-2), a critical T-cell growth cytokine, could be used to stimulate T cells designed with a synthetic receptor matching the synthetic IL-2. With this system, T cells can be manipulated even after they have been given to a patient by treating them with synthetic cytokine (which has no effect on other cells in the body). Intrigued by this work, Kalbasi and colleagues were interested in testing modified versions of the synthetic receptor that transmit other cytokine signals from the common gamma chain family: IL-4, -7, -9, and -21.
“It was clear from the outset that among the synthetic signals of the common gamma chain, the IL-9 signal was worth investigating,” said Kalbasi, adding that unlike other cytokines in the gamma chain. common, IL-9 signaling is not usually naturally active. T cells that occur. The synthetic signal IL-9 made T cells adopt a unique combination of stem cell and killer qualities that made them more robust to fight tumors. “In one of our cancer models, we cured more than half of the mice that were treated with synthetic IL-9 receptor T cells.”
Kalbasi said the therapy has been shown to be effective in multiple systems. They targeted two types of cancer models that are difficult to treat in mice: pancreatic cancer and melanoma, and used cancer cells to target T cells using the natural T-cell receptor or a chimeric antigen receptor. (CAR). “Therapy also worked if we gave the cytokine to the whole mouse and directly to the tumor. In all cases, the T cells designed with synthetic IL-9 receptor signaling were superior and helped us cure some tumors in mice when we couldn’t do it otherwise. ”
The drug, which mimics the virus, helps the immune system to target cunning cancer cells. More information: Anusha Kalbasi et al, Enhancing adoptive cell therapy through synthetic IL-9 receptors, Nature (2022). DOI: 10.1038 / s41586-022-04801-2 Provided by the University of California, Los Angeles
Citation: The study identifies a receptor that could alleviate the need for chemotherapy, T-cell therapy with previous radiation (2022, June 8) recovered on June 10, 2022
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