Sunday, June 26, 2022

CAR T-cell therapy targets cells that relieve leukemia

According to a preclinical study by Weill Cornell investigators, genetically engineered immune cells successfully target specific cancer cells, which may be responsible for relapse of a type of blood cancer, acute myeloid leukemia (AML) and disease. may prove effective in animal models. medicine. The new cell therapy, which is now being tested in phase 1 clinical trials, may eventually help patients with AML remain cancer-free.

In the study published on April 28 nature communication, The researchers used an approach in which immune cells known as T cells are directed to produce proteins called chimeric antigen receptors, or CARs, which enable T cells to recognize specific markers on cancer cells. makes. In this case, CAR is a receptor that binds to the CD123 molecule on leukemia stem cells, allowing T cells to seek out and attack cancer cells.

“Leukemia stem cells are a subset of leukemic cells that are resistant to standard chemotherapy drugs and may relapse in disease,” said co-senior author Dr. Monica L. Guzman, associate professor of pharmacology in medicine in the Department of Hematology and Medical Oncology, and member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. “CD123 is a marker found on leukemia stem cells, and my lab is working on creating a mouse model to test new CD123-targeted anti-leukemia therapies.”

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Although there are effective treatments to treat AML, the disease recurs in most patients after they achieve complete remission. By engineering T cells to express a CAR that targets CD123, Dr. Guzman and colleagues hope to rid patients of any remaining leukemia stem cells. CAR T cells are an attractive anti-cancer therapy because they can be grown in large numbers in the laboratory.

“The CAR T cells used in this study—called UCART123 cells—have several important features,” said Dr. Guzman. “They target leukemia stem cell markers, they are derived from healthy donors and manufactured ‘off the shelf’ and ready-to-go for patients when needed, they are specifically designed to reduce toxicity. It is designed to try, and they can be eliminated, using a drug called rituximab in case of excessive prevalence.”

When the team tested UCART123 cells in a mouse model of AML, they found that the therapy effectively eliminated leukemia cells and prolonged survival. The scientists also devised a highly-sensitive monitoring strategy to detect any residual cancer cells and assess the persistence of UCART123 cells. Finally, they showed that UCART123 cells have specificity against leukemia cells, with minimal toxicity to normal blood cells in mice.

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Preclinical results have led to the Phase 1 clinical trial trial UCART123 in patients with relapsed/refractory AML at multiple sites across the United States, including New York-Presbyterian/Weill Cornell Medical Center. “These laboratory data strongly support the ongoing clinical trial,” said the trial’s principal investigator and senior co-author Dr. Gail Roboz, director of the Clinical and Translational Leukemia Program at Weill Cornell Medicine and an oncologist at New York-Presbyterian/Weill Cornell Medical Center. ,

“Results from preclinical studies suggest that UCART123 cells are highly selective and specific in targeting AML, and we anticipate that the techniques developed in Dr. Guzman’s laboratory allow us to monitor and improve their success in patients receiving treatment with UCART123. Will help optimize the prospect,” he said. Dr. Roboz, who is also Professor of Medicine in the Department of Hematology and Medical Oncology and a member of the Mayer Cancer Center at Weill Cornell Medicine.

Reference: Sugita M, Galletto R, Zong H, et al. Allogeneic TCRαβ-deficient CAR T-cells targeting CD123 in acute myeloid leukemia. net common, 2022;13(1):2227. doi: 10.1038/s41467-022-29668-9

This article has been republished from material, Note: Content may be edited for length and content. For more information, please contact the cited source.

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