Linkage of Cancer and Lupus in Gliomas Patients
AGOURA HILLS, Calif., March 25, 2024 (GLOBE NEWSWIRE) — Oncotelic Therapeutics, Inc (OTCQB:OTLC) announced today the peer reviewed publication of Transforming Growth Factor Beta 2 (TGFB2) mRNA Levels, in Conjunction with Interferon-Gamma Receptor Activation of Interferon Regulatory Factor 5 (IRF5) and Expression of CD276/B7-H3, Are Therapeutically Targetable Negative Prognostic Markers in Low-Grade Gliomas: Past, Present, and Future Strategies in the Treatment and Management of Gliomas.
Dr. Vuong Trieu, CEO and Chairman of Oncotelic, stated, ”Our R&D team has discovered crosstalk between the TGF-β and IFN signaling pathways, linking gliomas and Systemic Lupus Erythematosus (SLE). This publication has identified IRF5 as a common target for both diseases, opening up a new avenue for combating cancer,”
Our findings place IRF5 at the intersection of inflammation and cancer. Understanding the role of IRF5 in both SLE and cancer opens an avenue for targeting IRF5 or its downstream pathways. This could offer new strategies for treating SLE and various cancers by modulating the immune response.
The article can be accessed for free online: https://www.mdpi.com/2072-6694/16/6/1202
Abstract:
Gliomas develop in the central nervous system from the glial cells that support it. Low-grade gliomas (LGGs) are characterized by a reduced number of immune cells infiltrating the tumor, requiring immune-boosting therapies to release the immunosuppressive environment of the tumor. We conducted a bioinformatics-led study to evaluate the prognostic impact of cell surface receptor markers for tumor-associated macrophages (TAMs) that produce transforming growth factor beta (TGFB) ligands and interferon-gamma receptor activation to maintain the tumor microenvironment in an immunosuppressed state. Detailed investigation of messenger RNA levels and their impact on OS in LGG patients demonstrated that low mRNA levels of a specific TGFB ligand, TGFB2, and the receptor along with the signaling molecules from interferon-gamma receptor activation (IFNGR2, IRF1, IRF5, and STAT1) result in improved survival of LGG patients. LGG patients expressing high levels of TGFB2 and IFNGR2 are over-represented in IDH wild-type tumor samples, suggesting that TGFB2 and IFNGR2 mRNA can be therapeutically targeted in these high-risk patients. Furthermore, demethylation of TFGB2, IFNGR2, IRF1, IRF5, STAT1, and CD276 genes also results in worse survival outcomes, pointing to a molecular mechanism that increases the negative prognostic effects of increased mRNA levels of these target genes. We observed that significant upregulation of mRNA expression levels for three TAM markers, MSR1/CD204, CD86, and CD68, suggested that TGFB2 is pivotal in establishing a pro-tumorigenic TME in gliomas mediated through TAMs. Interestingly, a tumor-associated antigen CD276/B7-H3 mRNA expression increased in tumor tissue, giving further insights into the roles of macrophages and tumor cells in the immunosuppressive TME. Therefore, to improve OS in LGG patients, combination therapies must target TGFB2 and IFN-γ activation (via IRF5 inhibition) or immune therapies targeted against CD276/B7-H3
About Oncotelic
Oncotelic (f/k/a Mateon Therapeutics, Inc.), was formed in the State of New York in 1988 as OXiGENE, Inc., was reincorporated in the State of Delaware in 1992, and changed its name to Mateon Therapeutics, Inc. in 2016, and Oncotelic Therapeutics, Inc. in November 2020. Oncotelic is seeking to leverage its deep expertise in oncology drug development to improve treatment outcomes and survival of cancer patients with a special emphasis on rare pediatric cancers. Oncotelic has rare pediatric designation for Diffuse Intrinsic Pontine Glioma (“DIPG” through OT-101) through its 45% joint venture, GMP Biotechnology Limited, melanoma (through CA4P), and Acute Myeloid Leukemia (through OXi 4503). Oncotelic acquired PointR Data Inc. in November 2019 to build an AI driven biotechnology company. Further, Oncotelic acquired AL-101, during the 4th quarter of 2021, for the intranasal delivery of apomorphine. We intend to develop AL-101 for the treatment of Parkinson Disease, erectile dysfunction, female sexual disorder and hypoactive sexual desire disorder. All these ailments have a very large population suffering from them and there is a need for treatments for each. For more information on AL-101, refer to our Annual Report on Form 10-K/A filed with the SEC on April 19, 2023.
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