On October 10, 2023 MAIA Biotechnology, Inc. (NYSE American: MAIA), a clinical stage company developing telomere-targeting immunotherapies for cancer, reported that its lead asset THIO showed highly potent anticancer activity in gliomas, an aggressive type of brain tumor that originates from glial cells (Press release, MAIA Biotechnology, OCT 10, 2023, View Source [SID1234635836]). THIO’s novel dual mechanism of action – direct telomere targeting and immune system activation, has previously demonstrated similar efficacy in multiple types of telomerase-active tumors.
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THIO was evaluated in various in vitro and in vivo models of gliomas. The results demonstrate the promising therapeutic role of THIO for the treatment of primary and temozolomide-resistant recurrent gliomas through specific telomerase-mediated induction of telomeric DNA damage in glioma cells
"High grade adult gliomas are among the most difficult-to-treat cancers, with less-than-desirable clinical outcomes. These encouraging results further highlight THIO’s excellent anti-cancer activity across several cancer indications," said Vlad Vitoc, M.D., MAIA’s Chief Executive Officer. "We look forward to evaluate THIO as a treatment for brain cancer in clinical setting."
"THIO was effective in the majority of human and mouse glioma cell lines with no apparent toxicity against normal astrocytes. As a monotherapy, THIO demonstrated efficacy in multiple glioma cell lines that had acquired resistance to the current state-of-the art care temozolomide (TMZ). THIO induced apoptosis in several human glioma cell lines that grow as three-dimensional tumor mass-mimicking neurospheres," said MAIA’s Chief Scientific Officer Sergei Gryaznov, Ph.D. "Additionally, THIO produced telomeric DNA damage responses not only in glioma cell lines, but also in diverse human-derived tumor specimens (PDXs). In vivo, THIO significantly decreased tumor proliferation in glioblastoma xenografts and a PDX model of glioblastoma."
The reviewed results were published in: Clin Cancer Res (2021) 27 (24): 6800–6814.
About THIO
THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) is a first-in-class investigational telomere-targeting agent currently in clinical development to evaluate its activity in Non-Small Cell Lung Cancer (NSCLC). Telomeres, along with the enzyme telomerase, play a fundamental role in the survival of cancer cells and their resistance to current therapies. The modified nucleotide 6-thio-2’-deoxyguanosine (THIO) induces telomerase-dependent telomeric DNA modification, DNA damage responses, and selective cancer cell death. THIO-damaged telomeric fragments accumulate in cytosolic micronuclei and activates both innate (cGAS/STING) and adaptive (T-cell) immune responses. The sequential treatment with THIO followed by PD-(L)1 inhibitors resulted in profound and persistent tumor regression in advanced, in vivo cancer models by induction of cancer type–specific immune memory. THIO is presently developed as a second or later line of treatment for NSCLC for patients that have progressed beyond the standard-of-care regimen of existing checkpoint inhibitors.