Health
Chimeric antigen receptor T cells targeting OR2H1 inhibit the growth of lung and ovarian tumors in mice-ScienceDaily
Chimeric antigen receptor T cell therapy (CAR T) has had a significant impact on the treatment of certain blood cancers, allowing patients with relapsed / refractory disease to lead longer and healthier lives. .. However, in clinical studies, cell therapy has been less successful in patients with solid tumors. This is because some tumor targets are not expressed in living tissue.In a new study published in Molecular cancer treatment drugResearchers at the Mofit Cancer Center, a journal of the American Association for Cancer Research, shared the identification of a new potential target for CAR T cells called OR2H1 and demonstrated that they inhibit the growth of lung and ovarian tumors.
The key to CAR T cell therapy is the genetic modification added to the patient’s T cells. These cells are collected through a process called apheresis and then sent to the laboratory where the cells are modified to contain genes for T-cell receptors that recognize specific markers on cancer cells. These modified T cells (now CAR T cells) are stimulated to grow and proliferate before being sent back to the hospital for injection into the patient. CAR T cell receptors act as GPS, looking for specific markers on the surface of cancer cells. Currently, there are CAR T therapies approved to treat patients with lymphoma, leukemia, and multiple myeloma, but no CAR T therapy approved for solid tumors.
Researchers at Moffitt are working to identify tumor markers that can make CART an effective treatment for patients with solid tumors. The goal is to find markers that are expressed in tumor cells but not in normal cells, reducing the potential for unwanted toxicity. The team, led by Dr. Jose Conejo-Garcia, focused on a family of proteins called olfactory receptors that are expressed in the nose and contribute to the sense of smell. During laboratory experiments, they found that the protein OR2H1 was expressed in a variety of solid tumors ranging from 4% of colon cancer samples to 69% of gallbladder cancers. Importantly, of all normal tissues examined, OR2H1 was detected only in the testis, suggesting that treatments targeting OR2H1 have minimal effect on normal cells.
Next, the researchers created CAR T cells that are specific for the OR2H1 protein. OR2H1 CAR T cells were able to kill lung and ovarian cancer cells that expressed OR2H1 but did not affect healthy cells. OR2H1 CAR T cells also showed antitumor effects in vivo in immunodeficient mice attacked with human tumors. Tumor suppression was observed in mouse models of lung and ovarian cancer with varying levels of OR2H1, including chemotherapy-resistant ovarian cancer cells.
These combined data suggest that OR2H1 may be an effective target for CART therapy in solid tumors. Researchers hope that these early studies will lead to the development of OR2H1CART cells for a wide variety of patients with solid tumors.
“Our study has broadened this treatment given the expression of OR2H1 in a subset of solid tumors across multiple histological types, including high-grade serous ovarian cancer, lung cancer, cholangiocarcinoma, prostate cancer, and ovarian cancer. Shows patient applicability. Multiple other histology. T cells to overcome immunosuppression in the tumor bed, as needed, by targeting molecules that are not expressed in important tissues. Can be further manipulated, “said Conejo-Garcia, chair of the Department of Immunology at Moffitt.
This work has been supported by the National Cancer Institute (P30CA076292, R01CA157664, R01CA124515, R01CA178687, R01CA211913, U01CA232758, T32CA009140, K99CA266947), the Mofit Foundation, Mofit’s Junior Scientist Research Partnership Awards, and the Postdoctoral Fellow of the American Cancer Society. rice field.
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material Provided by H. Remofit Cancer Center & Institute.. Note: Content can be edited in style and length.
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