THIO is a Telomere-by-Telomerase Targeting Agent in Development
For two decades now Telomerase was highly attractive, yet not extremely successfully pursued target in oncology. Chemical and structural modification, not shortening, of telomeres by telomerase, rather than inhibition of telomerase activity, is a new, recently introduced approach to specific cancer cell chromatin-targeted therapeutic approach. This new approach allows to completely eliminate the so-called “lag period in phenotypic responses” associated with the application of “classic” telomerase inhibitor(s).
Telomerase is present in >80% of human cancer cells and contributes significantly to proliferative abilities and immortality of cancer cells. It is either absent or shows very low activity in normal cells. THIO(6-thio-dG) is recognized by telomerase and incorporated into telomeres selectively in cancer cells. Once incorporated, it compromises telomere structure and function, leading to ‘uncapping’ of the chromosome ends resulting in rapid tumor cell death.
Only recently, in 2020, research by MAIA Biotech and the University of Texas Southwestern (UTSW), have identified never before observed immunogenic effects when low dose THIO is sequenced in advance of check-point inhibitors, the dominant standard of care immunotherapy.
MAIA Biotech plans to advance THIO to a Phase 1 clinical study in 2021.
Mender et al., Telomere Stress Potentiates STING-Dependent Anti-tumor Immunity, Cancer Cell (2020), https:// doi.org/10.1016/j.ccell.2020.05.020 https://www.cell.com/cancer-cell/fulltext/S1535-6108(20)30270-1
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