SRINAGAR: In a ground-breaking discovery, scientists have found a way to unlock the doors leading to the core of cancerous tumours, paving the way for more effective drug treatments. Researchers at the University of California, Davis, and Indiana University have identified a strategy that involves triggering a ‘timer bomb’ on the cells lining the blood vessels associated with tumours, ScienceAlert reported.
These blood vessels control access to the tumour tissue, and until they are opened, engineered immune cells struggle to reach the cancer for effective treatment. The ‘timer bomb’ is a ‘death’ receptor called Fas (or CD95), which, when activated by the right antibody, initiates the programmed death of the cell.
The scientists at UC Davis have pinpointed specific antibodies that, when attached to Fas receptors, effectively cause the cells to self-implode. This breakthrough is considered a potential therapeutic path for targeting Fas in tumours, a previously undervalued aspect in cancer immunotherapy.
By using these antibodies as a kind of “kill switch” for the cells, the researchers have demonstrated in experiments with mouse models and human cell lines that the immune checkpoint is opened, allowing other cancer therapies like CAR-T therapy to access more targets within the tumour.
CAR-T therapy involves programming a patient’s own white blood cells (T-cells) to target and attack specific cancerous cells. However, these engineered immune cells often struggle to penetrate the tumour’s microenvironments, particularly in solid tumours referred to as “cold tumours.”
The researchers at UC Davis have developed two engineered antibodies that proved highly effective in attaching to Fas receptors, causing bystander cells to self-implode. This success was observed in ovarian cancer models and various tumour cell lines tested in the laboratory.
The developed Fas ligand engaged two critical parts of the Fas receptor, holding significant potential as future drug targets. If CAR-T cells can be engineered to target these receptor parts on bystander cells, the therapy may become more effective against solid tumours.
Immunologist Jogender Tushir-Singh, the senior author of the study, emphasizes the importance of understanding a patient’s Fas status, particularly the mutations around the discovered epitope, before considering CAR-T therapy. This discovery not only serves as a definitive marker for the effectiveness of bystander treatment but also sets the stage for developing antibodies that selectively kill tumour cells, potentially supporting CAR-T-cell therapy in solid tumours.
