Viruses are tested for treatment of pancreatic cancer

2017-06-07

Pancreatic cancer is one of the most severe cancer types and the survival is only around one year, even if it is diagnosed at an early stage and despite surgery and chemotherapy. In a recent study from IGP the researchers have shown that a new type of immunostimulatory virus can kill cancer cells, stimulate immune cells and shape the tumour microenvironment. Clinical studies are on-going where the effect of the virus is tested patients with pancreatic cancer.

One reason for the failure of current therapies could be that the tumour consists of many cell types, besides the actual cancer cells. These cells are called stroma cells and they create a microenvironment in the tumour that affects the growth and spread of the cancer cells, and hampers drugs and immune cells from reaching the cancer cells.

Immunostimulatory virus therapy is a new promising strategy to treat cancer. In this method viruses are injected in the tumour where they multiply inside the cancer cells until the cells burst. The viruses are also genetically modified to have an immune stimulatory effect, which means that they produce substances that attract immune cells and stimulates them to attack the cancer cells.

In the present study the researchers have tested the immunostimulatory virus LOAd703, developed at IGP together with the Uppsala biotech company Lokon Pharma, to study its effect on cancer cells.

“We infected cultivated pancreatic cancer cells and could see that the cells died within 72 hours. We also injected viruses into tumours in mice that developed from human pancreatic cancer cells. When the injections where made in small tumours, tumour growth was completely abolished and also in larger tumours we could detect a decreased tumour growth,” says Angelica Loskog, who has led the study.

When viruses are injected in a tumour they will infect not only the cancer cells but also the stroma cells. The virus cannot multiply in the stroma cells but it can still produce substances that regulate these cells and thereby the tumour microenvironment.

“Stroma cells produce a number of compounds that stimulate cell division and affect metastasis. This is why the tumour microenvironment is so important for tumour development. When we infected stroma cells with LOAd703 the production of several of these compound decreased. It therefore seems as if the virus can modulate the microenvironment, which may even potentiate treatment with conventional therapeutics,” says Emma Eriksson, co-worker in Angelica Loskog’s research group.

The researchers also found that infection with LOAd703 led to an increased production of substances that stimulate immune cells, both in stroma cells and in cancer cells. Taken together the results show that injection of LOAd703 has both a tumour killing and immunostimulatory effect, and that this affects the tumour microenvironment. However, since the effect can be different in a growing tumour as compared to in cultivated cells or in mice, the mechanisms needs to be confirmed also in humans.

“We have initiated a clinical study together with our collaborator Baylor College of Medicine, and another one is starting in Uppsala in the autumn 2017 led by Gustav Ullenhag at Uppsala University Hospital. The Uppsala trial will include also other cancer types since LOAd703 is not specific for only pancreatic cancer. In the clinical trials we will investigate the safety and efficacy of repeated LOAd703 intratumoural injections combined with standard care. Eventually we hope that our finding will result in better survival for patients with cancer such as pancreatic cancer,” says Angelica Loskog.

The preclinical study was performed in collaboration with researchers in Barcelona and with the companies Lokon Pharma and Immuneed in Uppsala. The results have been published in the journal Clinical Cancer Research.
 

More information:
Paper in Clinical Cancer Research
Angelica Loskog’s research