Myrovlytis Trust Research Spotlight: Professor Mark Lowdell

In this blog we take a look at some of our research into BHD. Professor Mark Lowdell received research funding from the Myrovlytis Trust to look into natural killer (NK) cells and kidney cancer in BHD.

The Myrovlytis Trust is focussed on improving the lives of patients with BHD, many of whom develop renal cell cancer (RCC). Treatment options for RCC are limited and prognosis is poor.

In most cases of RCC, the tumour contains a lot of immune cells called lymphocytes, many of which are a particular 'cancer killing' lymphocyte called “Natural Killer” cells (NK). For over thirty years, patients with RCC have received treatments aimed at increasing the effectiveness of these NK cells. This results in clearance of tumour cells which remain after surgery and chemotherapy. However, most RCC patients relapse over time. People have been searching for better ways to enhance this immune response to help these patients.

In 2004, research from a team at University College London (UCL) found a new way to activate NK cells to kill tumour cells better.  This new way also does not cause the side effects associated with chemotherapy and some other immune cell activators. One of the UCL team developed the invention with a US biotec company to create a new drug. The new drug was based upon that original scientific research. The company named the new drug INKmuneTM and initially tested it in UK patients with leukaemia. The tests showed it to be very safe. In some cases, it activated NK cells in the patient so that they cleared cancer cells. This drug is in a clinical trial in metastatic prostate cancer at the moment. The major aim of this grant was to determine whether to conduct a UK trial in RCC patients. The US company provided the drug, some of the specialist equipment, and two of the staff who worked alongside the Myrovlytis Trust-funded scientist.

The research funded by this grant from the Myrovlytis Trust was performed by the UCL team which made the original discovery. It showed that for the first time NK cells from RCC patients could be primed to kill RCC tumour cells with INKmuneTM. This was the essential evidence for a clinical trial. Importantly, they found that not all RCC patients respond to INKmuneTM. This means that  patients can be screened before they enter the trial, so that only responsive patients are enrolled. This prevents RCC patients from being treated unnecessarily. It also makes a clinical trial much faster and more affordable.

Since the original discovery of NK cells and their ability to kill cancer cells, researchers around the world have realised that not all NK cells are the same. There are many subsets of these cells, and one type is called “memory-like” NK cell (mlNK) which are the NK cells best at killing cancer cells. No-one knows precisely what makes a mlNK cell, but research from this project has added important data to another project within the UCL group. It has led to a major scientific publication, helping the whole research community to better understand mlNK cells and point towards better ways to generate them. Most importantly, the Myrovlytis Trust project confirmed that INKmuneTM initiates the process driving NK cells to mlNK cells. It provides the essential data to submit an application to conduct a clinical trial of INKmuneTM in RCC patients.

This collaboration between a research focused charity, such as Myrovlytis Trust, UK academia, like UCL and a small biotec company, has been a great example of how to maximise the potential impact of charitable donations.