DKFZ Researchers Secure ERC Funding to Advance a "Lock-and-Kill" Gene Therapy for Glioblastoma
核心洞察
Moritz Mall's SafeCure project aims to equip glioblastoma (搜索) cells with the neuronal transcription factor MYT1L (搜索) to lock them in a low-plasticity, treatment-sensitive state.
The "lock-and-kill" strategy uses MYT1L (搜索) to stabilize cancer cells in a vulnerable state so chemotherapy and radiotherapy can kill them persistently.
AI-identified cancer-cell-specific enhancers will direct MYT1L (搜索) activity exclusively to glioblastoma (搜索) cells, minimizing off-target effects.
Glioblastoma (搜索), considered the deadliest brain tumor, has long frustrated drug developers because most therapies developed to treat it fail in clinical trials. A key reason for this failure is the "plasticity" of tumor cells, which can switch between different states and thereby evade treatment. Now, Moritz Mall, a division head at the German Cancer Research Center (DKFZ), is advancing a fundamentally novel gene therapy approach designed to overcome this challenge.
With the SafeCure project, Mall plans to equip glioblastoma (搜索) cells with the neuronal transcription factor MYT1L (搜索). This factor serves as a guardian of cell identity and keeps glioblastoma cells in a stable state of low plasticity by suppressing alternative gene programs. As a result, the cancer cells should become persistently sensitive to chemo- and radiation therapy. Mall and his team describe this as a "lock-and-kill" strategy: MYT1L locks the cells in a vulnerable state, and chemotherapy and radiotherapy kill them.
To ensure that MYT1L (搜索), administered via gene therapy, acts exclusively in cancer cells, Mall and his colleagues have devised another innovation. Using AI, they identified genetic enhancer elements that function only in cancer cells. The goal is to use these enhancers to specifically increase MYT1L activity in glioblastoma (搜索) cells, thereby limiting activity to the tumor while sparing healthy tissue.
The technology behind SafeCure is protected by patents. The project is expected to culminate in an investor-ready preclinical package that will enable pharmaceutical companies to bring SafeCure to its first use in humans.
Mall has been leading a research group since 2018 at the Hector Institute for Translational Brain Research (HITBR), a joint institution of DKFZ and the Central Institute for Mental Health (ZI) in Mannheim. The biologist completed his doctoral thesis at the EMBL in Heidelberg and subsequently conducted research at Stanford University in California.
The SafeCure project represents one of several ERC-funded initiatives at DKFZ aimed at improving cancer treatment. The German Cancer Research Center, Germany's largest biomedical research institute with more than 3,000 employees, identifies cancer risk factors, investigates how cancer progresses, and develops new cancer prevention strategies, as well as new methods to diagnose tumors more precisely and treat cancer patients more successfully.