UCLA researchers in the School of Dentistry have developed novel strategies synergizing the anti-tumor effects of a synthetic cannabinoid, cytokine, and probiotic bacteria to augments NK cell mediated functions and target a wide variety of cancers and viral infections.
BACKGROUND: Interest in the use of synthetic cannabinoids for the treatment of disease has grown in recent years in part because of the discovery that some tissue and cell types exhibit varying expression levels of cannabinoid receptors. Moreover, various cancers have now been found to abnormally increase the expression of these receptors as well, thus opening the possibility to better targeted therapies. While use of cannabinoid-based drugs for the direct treatment of diseases such as cancer is still nascent, research centered on synthetic cannabinoid WIN 55,212-2 have revealed that this compound can increase apoptosis and inhibit migration and invasion of the cancer in various contexts including osteosarcoma, epidermal tumors, prostate cancer, glioblastoma, melanoma, and breast cancer, among others. Initial research on these receptors is promising, but the full mechanism through which WIN 55,212-2 acts remains to be elucidated. Furthermore, secondary effects of WIN 55,212-2 need to be better characterized to inform the potential limitations of a WIN 55,212-2 focused treatments as well as to identify avenues for combination therapy.
INNOVATION: Researchers led by Dr. Anahid Jewett have elucidated the potential of WIN 55,212-2 as a novel therapeutic modality for various types of cancer due to its ability to augment NK cell functions and IFN-γ secretion. Using primary cells isolated from oral cancer patients and pancreatic cell lines, the researchers demonstrated that WIN 55,212-2 inhibits tumor progression and induces cell death. They validated these results by quantifying expression of four surface markers, which helped to differentiate between cancer stem cells or poorly differentiated tumor cells, moderately differentiated tumor cells, and well-differentiated tumor cells. From in vitro and in vivo murine model studies, the researchers discovered that WIN 55,212-2 was particularly effective in targeting cancer stem cells (CSCs) and poorly differentiated tumor cells, a cell type that is resistant to chemotherapy, by increasing the cytotoxic function of NK cells. In a few specific scenarios, WIN 55,212-2 increased the expression of programmed cell death ligand 1 (PD-L1), suggesting promising avenues for combination treatment approaches; the researchers demonstrated the efficacy of this synergistic approach with cytokines and probiotic bacteria in murine models. Taken together, a novel drug that targets CSCs/poorly differentiated tumor cells could help treat patients with aggressive and metastatic tumors.
POTENTIAL APPLICATIONS:
- Treatment for a variety of aggressive and metastatic tumors, including oral and pancreatic cancers
- Combination therapy to augment NK cell-mediated functions in cancer and virally infected patients
ADVANTAGES:
- Increased cytotoxic function of NK cells
- Augmented IFN-γ activity
- Targets a subset of tumors composed of cancer stem cells and ‘stem-like’ tumor cells that cannot be targeted through chemotherapy
DEVELOPMENT-TO-DATE: The researchers have demonstrated success of the cannabinoid in inhibiting tumor progression in vitro with primary cells and cell lines, and in vivo in murine models. The researchers have also shown efficacy of the drug in combination with cytokines and probiotic bacteria for treating tumors in murine models.
Related Papers (from the inventors only):
Meng-Wei Ko, Barbara Breznik, Emanuela Senjor, Anahid Jewett. Synthetic cannabinoid WIN 55,212–2 inhibits growth and induces cell death of oral and pancreatic stem-like/poorly differentiated tumor cells, Advances in Cancer Biology - Metastasis, Volume 5, 2022, https://doi.org/10.1016/j.adcanc.2022.100043.
KEYWORDS: Cancer, Synthetic Cannabinoid, Cannabinoid, oral cancers, pancreatic cancers, cancer stem cells, NK cells, IFN-γ