A clinical trial in the UK will test for the first time a precision therapy for pancreatic cancer, which is one of the deadliest cancers and for which treatments have remained largely unchanged for decades.   

Precision medicine uses the genetic characteristics of a patient’s tumour to define the treatments, improving outcomes and reducing side effects. These advances have been made possible due to decades of basic and translational research, including research in animals that allowed the development of strategies to tackle cancer. 

The PemOla trial at Addenbrooke’s Hospital in Cambridge combines two drugs – pembrolizumab, an immunotherapy for cancer, and olaparib, already used as a treatment for tumours with changes in the BRCA genes. These genes, known for their role in breast and ovarian cancer, are also linked to an increased risk of other cancers, such as pancreatic cancer, prostate cancer and melanoma.  

Pembrolizumab is widely used to treat several cancer types. It was first studied in humanised mice – mice that mimic human immune responses to cancer – and was shown to help the immune system to recognise and attack cancer cells. Olaparib was first developed for ovarian, breast and colorectal cancers, but it has since been shown to be effective in other cancers, including pancreatic cancer. It was originally tested in mice, where it was shown to kill cancer cells by preventing the repair of DNA damage.  

“Pancreatic cancer remains one of the hardest cancers to treat with very few available treatment options,” said Dr Pippa Corrie, oncologist and leader of the trial. “For the first time we’re taking a precision immunology approach to treatment, which we hope will have a transformative effect for the patients that are able to benefit.”  

Researchers in the US have been able to safely generate CAR-T cells within the body of mice, possibly solving major limitations of this therapy, which revolutionised the treatment of many blood cancers. 

CAR-T cell therapy requires that a patient’s own T cells – a type of immune cell – are collected from the body, genetically altered to detect and kill cancer cells and returned to the patient. This is a week’s long process that is labour-intensive and expensive. 

Researchers at Stanford Medicine, California, took advantage of the same technique used for mRNA-based vaccines to generate CAR-T cells in mice directly. 

The researchers created tiny soluble bubbles, called nanoparticles, with an antibody on their surface that made them attach specifically to T cells, delivering instructions for the T cells to find and kill B cells, which grow uncontrollably in many blood cancers.  

These nanoparticles, when injected into mice with a type of B cell blood cancer, were able to generate internally a similar number of CAR-T cells to the one administered to patients undergoing the conventional therapy. These cells were also able to travel to the tumours. Six out of eight mice were tumour-free after 60 days of treatment and tumour growth was controlled in the remaining two. 

"The combination of safety and efficacy we've seen in the mice is impressive," said Katherine Ferrara, leader of the study published in PNAS.  

Conventional CAR-T cell treatment requires that the patients undergo a process to reduce the number of remaining T cells, which increases the efficacy of the therapy but makes them susceptible to infections. This new strategy does not require this procedure, possibly making CAR-T cell therapy not only cheaper, faster and available to a greater number of patients, but also safer.