Genetic ablation of quiescent cancer cells through DTA-p27
Introduction
Quiescence is essential for cancer cells to survive in a new environment and initiate metastasis, to become resistant to cancer therapy, and to evade immune destruction. The plasmid expressing DTA-p27 reduces the number of quiescent cancer cells and infiltrated cancer cells in a mouse model of high-grade glioma. Furthermore the plasmid expressing DTA-p27 increases the survival of a mouse model of high-grade glioma (Antonica et al., Nature Communications 2022, doi: 10.1038/s41467-022-32448-0).

Technical features
The plasmid expressing DTA-p27 reduces the number of quiescent cancer cells and infiltrated cancer cells in a huma organoid model of high-grade glioma. Furthermore the plasmid expressing DTA-p27 increases the survival of a mouse model of high-grade glioma (Antonica et al., Nature Communications 2022, doi: 10.1038/s41467-022-32448-0). We start from a TRL4 with the technology tested in the laboratory. In the next 12 months we will arrive at a TRL of 5 with the validation of DTA-p27 function with a viral infection in human brain organoids grown in vitro.
Possible Applications
- Adult Glioblastoma;
- Pediatric high-grade Glioma;
- Human Metastasis.
Advantages
- Chemotherapy is not able to kill quiescent cells. Our DTA-p27 construct is able to kill quiescent cancer cells;
- PROM1 and CDKN1B (P27KIP1) are not expressed in mature neurons or astrocytes. Therfore our technology is able to kill only cancer quiescent cells.