New targeted therapy against osteosarcoma

A new target for CAR therapy against osteosarcoma has been discovered in the Translational Research Unit at the Department of Cellular Therapy (Olso University Hospital). The results of their research, which was completed in the laboratories of Oslo Cancer Cluster Incubator, were recently published in an article in Nature Communications.

“CAR is a new type of molecule. It stands for Chimeric Antigen Receptor. It is part of a bigger family of cancer treatments called immunotherapy, in which you use the immune system of the patient to fight cancer,” explained Sébastien Wälchli, who has co-led this research project with Else Marit Inderberg.

A unique molecule

Chimeric antigen receptor therapy (CAR T) is a cancer treatment in which a patient’s T cells (a type of immune cell often referred to as the “foot soldiers” of the immune system) are changed in the laboratory so they will attack cancer cells.

“In the case of the CAR, we help the immune system to recognize cancer cells by putting in a completely artificial receptor. The key part of the receptor is the recognition site, so it will guide the immune cell to the tumour. Normally, we need a molecule that can recognize a cancer marker. The molecule of choice is an antibody,” said Wälchli.

The antibody that Wälchli’s group used was first isolated by clinical researcher and sarcoma expert Prof. Øyvind Bruland in 1986.

”We designed the CAR based on this antibody by using its coding sequence. This antibody is quite unique because it recognizes the marker on the surface of lung metastasis of osteosarcoma. We created a Osteosarcoma CAR (OSCAR) molecule to see if we could use the power of this antibody in immunotherapy and the results published in Nature Communications prove that we can,” explained Wälchli.

A full preclinical validation

The preclinical development of the treatment took place in the laboratories of Oslo Cancer Cluster Incubator which are fully equipped for such a process.

“We did a full preclinical validation of OSCAR using devices installed at the incubators for the in vitro and further tested it in vivo using different animal models where we mimicked what would happen in human. Our colleagues in Barcelona tested the injection of tumour cells directly into the bone of mice and observed a lower progression of cancer in the mice treated with OSCAR T cells, than we,” said Wälchli.

Furthermore, the group did experiments to check the toxicity of OSCAR T cells.

“We tried to predict using different healthy tissues if this CAR would only recognize tumour cells and spare healthy tissues. We concluded that it was safe, but before you inject it in human, you will never know for sure,” said Wälchli.

What is osteosarcoma?

Osteosarcoma is a bone cancer and affects many children and older people. It is quite well-treated with chemotherapy, but when it metastasizes to the lungs, it becomes more difficult to treat. Surgery can slow down the progression, but the cancer can reappear.

“This is where our hearts brought us. We are not choosing cancer by patient. We always talk with the clinicians. When we first discussed with Bruland, we did not know much about osteosarcoma. He told us about patients who have absolutely no alternative,” Wälchli explained.

There are other CARs in development against osteosarcoma globally, and some have already reached clinical phase, but none cover all patients.

“In the seminal paper of Bruland in 1986, they checked the biobank and estimated that 90 per cent of all osteosarcoma patients were positive to this antigen. This was confirmed by our collaborators in Spain. According to the first estimate, it looks like this marker is the most important that has been described so far,” said Wälchli.