Oncology, Immunology
Turning Melanoma Cells Against Themselves as the Next-Generation Immunotherapy
2023 Harrington Scholar-Innovator
A powerful cancer-fighting gene therapy platform that can detect cancer cells and then “reprogram” those cells to produce anticancer therapeutics could usher in a new era in the detection and treatment of melanoma and other common cancers.
According to Dr. Wu, many cancer researchers aim to target transcription factors, which initiate and regulate the process of tumor formation.
“If you think of the body’s cells as machines, each machine would have around 1,800 knobs (transcription factors) that could be adjusted to make it perform a certain way,” Dr. Wu explained. “Hence, transcription factors are the main culprits that drive tumor formation. However, they are structurally dynamic, making them challenging to target.”
Dr. Wu and his colleagues have developed a programmable Synthetic Transcription-factor Activity Responsive (STAR) gene circuit platform that can turn aberrant transcription factor activity into therapeutic response. Dr. Wu’s lab is leveraging the STAR gene circuit to educate patients’ own immune systems to kill tumor cells. Gene circuits (highly engineered DNA sequences that work together), delivered systemically, are activated by the presence of cancer-specific transcription factors. The cancer cells are then forced by the activated gene circuits to produce cancer-fighting immunomodulators.
“We were able to develop a comprehensive sensor library that covers almost all known human transcription factors, and this sensor platform has turned out to be a very good weapon to distinguish tumor cells from normal cells,” Dr. Wu said.
In mouse models in vivo, STAR has elicited a strong immune response against melanoma. This therapy also holds promise for ovarian, prostate, and breast cancer, Dr. Wu added.