A hard-to-treat cancer with no target to detect... New treatment avenue opens by implanting a ‘target’ in cancer cells

[Financial News] A new technology has been developed to treat hard-to-treat cancers that existing immunotherapy drugs could not tackle because immune cells have difficulty detecting them. It uses an artificial genetic device to create ‘immune targets’ directly in cancer cells. The technology is expected to open up new treatment possibilities for patients with malignant bone tumors, who have had few options beyond surgery.
A team led by Professor Kim I-jun of the Department of Medicine at Ewha Womans University, in collaboration with Professor Kim Jin-hong of Seoul National University and a team led by Professor Ming-Ru Wu of the Dana-Farber Cancer Institute in the United States, developed a combination immunotherapy technology that generates immune targets in cancer cells and blocks factors that interfere with the immune system, the team announced on the 23rd. The findings were published in the latest issue of the international journal Trends in Biotechnology.
Chondrosarcoma, a malignant tumor that develops in bone, is a notoriously hard-to-treat cancer that metastasizes quickly and responds poorly to chemotherapy or radiation therapy. The 10-year survival rate for patients who cannot undergo surgery or whose cancer has spread to other organs is below 30%. In particular, immunotherapy drugs, now widely used to treat cancer, find cancer cells by recognizing ‘targets (antigens)’ on their surface for immune cells to attack. Chondrosarcomas have very few of these targets, however, making it difficult for immune cells to recognize the cancer.
Rather than searching for new targets, the research team found a breakthrough using ‘gene circuit’ technology that makes cancer cells produce targets themselves. After identifying a type of ‘genetic switch’ that operates specifically in chondrosarcoma cells, the team designed a fail-safe circuit that activates only when both of two switches are turned on. When the circuit activates, it leaves normal cells untouched and produces therapeutic proteins that attract immune cells only in chondrosarcoma cells.
The team also applied a treatment that combines this approach with an antibody that blocks MIF, an inhibitory substance released by cancer cells to fend off attacks by immune cells. When both treatments were administered to laboratory mice with functioning immune systems, the tumors shrank markedly. In particular, the researchers confirmed a ‘distant treatment effect’: although the drug was injected into only one tumor, metastatic tumors on the opposite side also shrank, despite not receiving the treatment directly.
Professor Kim I-jun of Ewha Womans University explained, “This study demonstrates the potential for systemic immunotherapy for patients with chondrosarcoma, who have had limited options beyond surgery,” adding, “The technology could also be applied to other hard-to-treat cancers for which immunotherapy has been difficult due to a lack of targets.”  

[email protected] Kim Man-gi Reporter