On April 18, 2023 MAIA Biotechnology, Inc. (NYSE American: MAIA) reported the peer-reviewed publication of original research article in this month’s issue of Molecular Cancer Therapeutics (volume 22, issue 4), a renowned American Association of Cancer Research (AACR) (Free AACR Whitepaper) journal that publishes translational research studies focused on the discovery and preclinical development of therapeutic agents for oncology (Press release, MAIA Biotechnology, APR 18, 2023, View Source [SID1234630290]). The preclinical study, entitled "Activating an Adaptive Immune Response with a Telomerase-Mediated Telomere Targeting Therapeutic in Hepatocellular Carcinoma," showed highly potent anticancer activity of THIO in multiple HCC preclinical models.
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The study revealed the anti-tumor immune response role of THIO as a telomerase-dependent telomere targeting therapeutic in HCC models. THIO induces telomere damage and activates the cGAS-STING pathway, which is a major intracellular signaling pathway that plays a role in innate immune responses. THIO enhances the cross-priming capacity of dendritic cells (DCs), which are antigen presenting cells of the adaptive immune system and activates tumor specific T cells. Observed potent anticancer activity is taking place in CD8-positive T cell dependent manner. Moreover, the study showed a potential role of immunogenic protein molecule HMGB1 (high-mobility group box 1, which are released during cancer cell death), in THIO induced T cell activation. In addition, the study demonstrated enhanced efficacy and durability of complete tumor regression when THIO is followed by administration of immunotherapies (an anti-PD-1 or anti-PD-L1) and anti-VEGF (anti-vascular endothelial growth factor, one of the major anti-angiogenic drug target) in advanced, resistant HCC tumors providing a strong scientific rationale for a clinical trial in HCC.
"The knowledge gained from this study will help support our understanding of the compound’s mechanism of action and its broad therapeutic utility. Moreover, this publication strengthens our scientific rationale already included in our current clinical development plan for THIO-102, a Phase 2 clinical study in multiple solid tumor indications, including HCC," said MAIA’s Chief Scientific Officer Sergei Gryaznov, Ph.D.
"The findings from our study provides solid rationale for THIO to be evaluated as a treatment of liver cancer, as our Company already holds the US FDA Orphan Drug Designation for this clinical indication. This published evidence supports our strong belief that THIO, especially in combination with immune checkpoint inhibitors and other standard of care agents, may be clinically studied for treatment of various forms of cancer," added Vlad Vitoc, M.D., MAIA’s Chief Executive Officer.
The full results are available in Molecular Cancer Therapeutics and online here.