Immunotherapy of cancers

Many have heard about immunotherapy, but its workings and benefits may not always be clear.

Immunotherapy is the term used for when the patient’s own immune system is being supported to beat a disease, like cancer. Scientist have known for a long time that an infection could cure cancer.

The earliest evidence that an immune response could cause disappearance of cancer came from Italy around 1300, when a priest named Peregrine Laziosi noticed his tumour disappear after a severe infection in the tumour site. One of the earliest active cancer therapies is from the late 1800s, when Dr. William B. Coley of New York City injected bacteria into tumours and saw that those tumours then often disappeared. Even though this had some success, research in both cancer and immunology has come a very long way since then, and immunotherapy has now become a major strategy for treating cancer. Still, for most cancers, the immune response does not become strong enough to fully eradicate the tumour without further help. Therefore, researchers are attempting various new ways of strengthening the immune system’s attack or making it more directed towards the cancer.

The type of tumours that do survive attacks by the immune system have developed their own strategies to avoid destruction by creating a local environment around the tumour that weakens the immune cells. This is a major obstacle for effective eradication of the tumour, even if there is a strong immune attack.

Though there are existing and developing immunotherapies that try to counteract this defence system of the tumours, in many cases, there is not enough immune activity towards the cancer cells. Basically, because there are not enough anti-cancer cells, and the ones that can do the job, quickly become tired and exhausted from too much work.

In those cases, one can try to replicate effective anti-cancer cells outside the body and then injecting them back. This is called adoptive cell transfer or ACT immunotherapy. Cells from the patient are used: either tumour-reactive immune cells that doctors retrieve from the tumour site, or by creating from the patient’s own blood new immune cells that are genetically modified to specifically target the tumour. In either case, patient’s own cells are collected, activated and expanded prior to re-infusion into the patient’s blood.

These new specifically tailored “anti-cancer cells” are very good at attacking so called “blood cancers” or leukaemia’s, where the cancer cells are distributed around the tissues and don’t really form larger tumours of any significant size. But for most tumours, the cancer cells grow in lumps and the adoptively transferred cells are not so apt at chewing through the entire mass of this tumour, hence becoming tired and exhausted and stop working after a while, before all cancer cells have been eliminated.

And that is exactly what the INCITE project is trying to do something about: making anti-cancer cells that are better at fighting these solid tumour lumps. So, what do we ideally want to make?

Anti-cancer T cells that can be (I) easily replicated and (II) that endure the long-lasting battle against a constantly growing tumour. In order to realise this, we take the current knowledge to the next level: we want to create very specific “anti-cancer memory cells”. These cells would need to have the ability to replicate fast, and hence helping to build a large army to attack the tumour. And they also are robust and have the endurance to fight for a long time.

These “anti-cancer memory cells” naturally originate from immune niches within lymph nodes, but are not mobilised quickly enough, within the numbers needed to get rid of the tumour.

Immunotherapy could support the growing of these cells but need immune niches to grow them. That is exactly what INCITE is working on: creating these immune niches in the laboratory, to make the necessary long-lasting anti-cancer memory cells, that can support the continuous generation of anti-cancer killer cells to fight the cancer! We could then provide patients with the best workforce to eradicate the tumour mass over time. This is however not an easy task, and we need all the help we can get.

So, the INCITE partnership has assembled a team to make this niche. This involves mathematical modelling, material science and 3D printing, but also team members to analyse natural occurring niches as well as the niches we make ourselves, to give ideas and input for creating this niche. It will be exciting to investigate if we can make better anti-cancer cells in the future than the ones used already today.