Increasingly common with immunotherapy against cancer

A study has been underway at the University Hospital since the spring of 2018, in which a virus is used as a carrier of immune-stimulating genes. The target group is patients with non-operable cancer originating in the pancreas, colon and rectum, bile ducts or ovaries.

For cancer patients, immunotherapy is increasingly seen as the fourth cornerstone of the treatment arsenal alongside surgery, radiation therapy and chemotherapy.

- The hope is that the treatment will prove effective, without causing severe side effects, and thus can be registered as a drug for clinical use, says Gustav Ullenhag, chief physician and associate professor at the cancer clinic, Akademiska sjukhuset and researcher in translational immunotherapy, Uppsala University.

Cancer cells burst

The researchers use a so-called oncolytic virus, which was developed by Professor Angelica Loskog's research group at Uppsala University together with a pharmaceutical company.

The virus carries genes for immune-stimulating substances, and is injected repeatedly into the tumor. This causes cancer cells to rupture and stimulates the immune system to attack the cancer, hopefully even metastases that have not been injected.

The study began in the spring of 2018 and is expected to last until 2021. A total of over 40 patients will participate, all of whom have advanced (non-operable) cancer originating in the pancreas, bile ducts, colon / rectum or ovaries. The immunostimulatory gene therapy is given as a complement to the chemotherapy treatment they would otherwise have received.

Eight injections into metastases

- We have previously evaluated safety. This autumn, Phase II will begin, which means that all patients receive the dose that is best assessed and that we evaluate how effective the cancer treatment is, says Gustav Ullenhag.

The participants in the study receive a total of eight injections every two weeks in metastases (daughter tumors). The injections are given ultrasound-guided by the radiologists. The effect is measured with the help of X-ray examinations, but the researchers also examine immunological responses in both blood and metastases.

Advances in immune and gene therapy

In 2018, the Nobel Prize in Medicine went to researchers James P Allison and Tasuku Honjo, who were rewarded for the discovery of cancer treatment by inhibiting the immune system's braking mechanisms.

So-called immune checkpoint inhibitors, which bind to and block inhibitory proteins on T cells, are now an established treatment for several cancers, especially malignant melanoma.

Top left: To activate T cells, the T cell receptor needs to recognize a foreign structure bound to a so-called antigen-presented cell. Activation also requires the T-cell accelerator pedal. CTLA-4 acts as a brake that can prevent the accelerator pedal from functioning. Bottom left: Allison discovered that antibodies to CTLA-4 inhibit the function of the brake, leading to the activation of the T cell so that it can attack cancer cells. Top right: Honjo discovered another brake (PD-1) that inhibits T cell activation. Bottom right: Antibodies to PD-1 inhibit brake function, leading to T cell activation. The result is a very effective attack on cancer cells. Source: nobelprize.org

Another example of immunotherapy is Car T cell therapy which is about modifying the body's immune system. Academic was the first in Europe to offer treatment for lymphoma and leukemias and it is now registered and approved within the EU.