A Novel Potential Target for CAR-T Cell Therapy in Human Solid Tumors Discovered
At present, chimeric antigen receptor T cell therapy (CAR-T) has made significant achievements in the treatment of specific hematological cancers, allowing patients with relapsed/refractory disease to survive longer and become healthier, but in clinical studies, cell therapy has actually not been successful in the treatment of patients with solid tumors, in part due to the lack of tumor targets expressed in important tissues. Recently, in a study published in Molecular Cancer Therapeutics entitled 'Olfactory Receptor OR2H1 is an effective target for CAR T cells in human epithelial tumors,' scientists from Moffitt Cancer Research Center identified a novel potential target for CAR-T cells called OR2H1 through research, which may help inhibit the growth of lung and ovarian cancers.
The key to CAR-T cell therapy is the genetic modification of a patient's body's T cells, which can be collected through a process called apheresis and then shipped to a laboratory, where the cells are modified to contain T cell receptors that recognize specific markers on the surface of cancer cells. The newly modified T cells (CAR-T cells) are stimulated to grow and multiply before being infused back into the patient. The receptors on the surface of CAR-T cells can act as a GPS, looking for special markers on the surface of cancer cells; a variety of CAR-T cell therapies have been approved for the treatment of patients with leukemia, lymphoma and multiple myeloma, but there are currently no CAR-T cell therapies approved for the treatment of solid tumors.
At present, researchers are working hard to identify tumor biomarkers to promote CAR-T cell therapy to more effectively treat solid tumors. The goal of researchers is to find a marker that is expressed in tumor cells but not in normal cells. 'We focused on a family of proteins called olfactory receptors, which are expressed in the nasal cavity and promote olfactory perception,' said researcher Jose Conejo-Garcia. During the period, the researchers found that the OR2H1 protein was also expressed in a variety of solid tumors, including 4% of colon cancer samples to 69% of gallbladder cancer samples. Importantly, OR2H1 was only found in the testis of all normal tissues examined, which may suggest that therapies targeting OR2H1 may have little effect on normal cells.
Subsequently, the researchers developed CAR-T cells with specificity for OR2H1 protein. OR2H1 CAR-T cells can kill lung cancer and ovarian cancer cells expressing OR2H1, but have no effect on healthy cells. In addition, OR2H1 CAR-T cells also have certain anti-tumor effect in immunodeficient mice challenged with human tumors. In lung cancer and ovarian cancer mouse models with different OR2H1 levels, the researchers observed certain tumor inhibitory effect, including ovarian cancer cells resistant to chemotherapy. These comprehensive data suggest that OR2H1 may be expected to be an effective target for CAR-T cell therapy for the treatment of solid tumors, and researchers hope that these initial findings will help develop OR2H1 CAR-T cells for patients with a variety of solid tumors.
Researcher Conejo-Garcia said that given that OR2H1 can be expressed in a variety of histological solid tumor subtypes (including high-grade serous ovarian cancer, lung adenocarcinoma, cholangiocarcinoma, prostate cancer and ovarian cancer with other histological characteristics, etc.), the results of this study confirm that this novel therapy may have some applicability to patients with a variety of cancers, and targeting a special molecule that is not expressed in key tissues may hopefully help researchers engineer T cells to overcome the immunosuppressive effect of tumors. In summary, the results of this study suggest that redirected T cells against OR2H1-expressing tumor cells may represent a potential cancer therapy that may be expected to treat a variety of epithelial cancers while possibly producing the toxic effects brought about by some acceptable therapies.
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