Scientists have identified a new synthetic molecular code that could improve a patient’s response to an effective cancer treatment, known as PD-1 blockade immunotherapy. The team from Kyoto University have created a new molecular code that ensures a supply of energy to cancer-killing T-cells. The molecular code is highly effective at targeting cancer cells when combined with PD-1 blockade immunotherapy, offering exciting potential for clinical use in the future. 

T cells in the body target cancer directly, but cancer cells fight back, expressing a molecule known as PD-L1 that can “inactivate” them. Scientists have developed highly effective immunotherapies that stop PD-L1 from targeting T-cells, but they don’t work in all patients. 

“One of the major reasons for this unresponsiveness is that these patients have an insufficient number of T cells that also become exhausted because they don’t have enough active energy-providing mitochondria,” explains Ganesh Namasivayam, one of the authors of the study and Pandian of Kyoto University’s Institute of Integrated Cell Material Sciences (iCeMS). 

In new research, published in the Cell Chemical Biology, the team describe how they have developed an exciting new way to increase the mitochondria in T-cells, improving the effectiveness of PD-L1 immunotherapies. They focused on activating the molecule PGC-1 that plays a crucial role in gene expression. The team engineered a compound known as pyrrole-imidazole polyamide (PIP) to target the specific DNA sequence to activate PGC-1. 

The new molecular code developed by the team, known as EnPGC-1, was tested in mice, where it increased the numbers of T-cells and their longevity. The team then gave mice with tumours a combination of EnPGC-1 and PD-1 blockade immunotherapy. The results improved anti-tumour immunity and survival rates, demonstrating the clear potential for EnPGC-1. 

The researchers are optimistic about the future of EnPGC-1, says study author Madhu Malinee. “Since PGC-1 signaling is known to be essential for energy metabolism, EnPGC-1 also has potential for being developed as a drug to treat other diseases, like type 2 diabetes and hyperlipidemia.” 

Years of further testing and development are required before EnPGC-1 could enter clinical trials, caution the authors, but there is clear potential for EnPGC-1 to improve cancer immunotherapies. 

RGCC scientists are at the forefront of developing new combination immunotherapies that help the body target and treat cancer. Recently published research by RGCC scientists has included developing a new novel small molecule inhibitor to increase breast cancer cell sensitivity and creating a new Genistein dietary supplement that’s 34% more effective than currently available commercial alternatives.  

Alongside pioneering research, RGCC offers a range of genetic tests designed to provide crucial information for clinicians on cancer diagnosis and treatments. For example, our Immune-Frame test provides medical professionals with essential information about the strength of a patient’s immune system. Onconomics Extracts can highlight natural substances and plant extracts that could improve your ongoing treatment for patients with cancer. 

You can learn more about RGCC’s range of genetic tests here.

You can read the full paper, Targeted epigenetic induction of mitochondrial biogenesis enhances antitumor immunity in mouse model, here.