To modify CAR T-cells to target and kill neuroendocrine tumor cells, a method that has had dramatic results in patients with other cancers. Success in this project could pave the way for trials of this breakthrough technology for neuroendocrine tumors.
The Caring for Carcinoid Foundation is pleased to announce this grant, part of a multi-pronged strategy to harness the potential of the breakthrough field of immunotherapy to treat patients with neuroendocrine cancer.
This project relies on the expertise of Carl June, MD, renowned for his work in immunotherapy. In particular, Dr. June’s team spent many years developing CAR T “serial killer” T cells, which have been very successful in clinical trials treating patients with forms of leukemia and other cancers.
This project brings together the multi-disciplinary team of Xianxin Hua, Carl June, and David Metz to develop CAR T cells to target receptors found on neuroendocrine tumor cells and then kill those cells.
Generate and optimize somatostatin receptor specific CAR T cells that target the surface of human neuroendocrine tumors.
Test the anti-tumor activity of anti-SSTR2 or SST-ligand CAR T cells in vitro.
There is a critical need to develop better treatments for patients with neuroendocrine tumors. A salient feature for many neuroendocrine tumors is the abnormally high level of somatostatin receptors on the surface of the tumor cells. Octreotide, a long acting analog of normal hormone somatostatin, and other similar derivatives have been long used to target somatostatin receptors on tumor cells to suppress the secretion of hormones from the tumor cells and growth of tumors. But Octreotide and its derivatives rarely kill tumor cells and reduce tumor mass. Tragically, 5-year survival for metastatic neuroendocrine tumors remains very low. Therefore, it is highly desirable to develop new and more effective therapies for patients with neuroendocrine tumors.ine tumors.
Recently, adoptive T cell therapy involving engineered chimeric antigen receptors (CARs), which specifically target tumor associated antigens, has been reported to successfully eradicate human chronic lymphocytic leukemia and prevent its recurrence. These recent advances raise an exciting and real possibility that neuroendocrine tumor cells can be targeted and killed to improve the treatment of patients with neuroendocrine tumors. We will first develop CAR T cells designed to eradicate neuroendocrine tumors via targeting somatostatin receptors on the surface of the neuroendocrine tumor cells. Second, the best CAR T cells will be tested for their capability to specifically kill the cancer cells in cultured cells.
These studies will aid the development of an entirely new and effective therapy for neuroendocrine tumor patients who have failed previous treatments.
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