Healthcare, UK (Commonwealth Union) – Researchers at UCL have developed a new type of immunotherapy that has shown promising preclinical results against osteosarcoma, a bone cancer, in a study conducted on mice.
Osteosarcoma which is the most common bone cancer in teenagers but remains relatively rare, with around 160 new cases annually in the UK. In contrast, over 150,000 people suffer from cancers that have metastasized to the bones.
Researchers of the study highlighted the facts that bone-related cancers are particularly challenging to treat and are a leading cause of cancer-related deaths. These cancers often exhibit resistance to chemotherapy, underscoring the need for new treatment options.
The study, published in Science Translational Medicine, discovered that a specific subset of immune cells known as gamma-delta T cells (gdT cells) could offer an effective and economical treatment solution.
gdT cells are a less familiar type of immune cell derived from healthy donor immune cells. They possess potent innate anti-cancer properties, can target and kill antibody-labeled cancer cells, and can be safely administered from one person to another without the risk of graft-versus-host disease.
To manufacture the cells, blood is taken from a healthy donor. The gdT cells are then engineered to release tumor-targeting antibodies and immune-stimulating cytokines, before being injected into the patient with bone cancer. This new treatment delivery platform is referred to as OPS-gdT.
Researchers evaluated the treatment on mouse models with bone cancer and found that OPS-gdT cells outperformed conventional immunotherapy in regulating the growth of osteosarcoma.
Lead author, Dr. Jonathan Fisher (UCL Great Ormond Street Institute of Child Health and UCLH), pointed out that the present immunotherapies, such as CAR-T cells (which use genetically modified immune cells from the patient), are expensive and time-consuming, allowing the patient’s disease to progress. Dr. Fisher further indicated that although effective for leukemia, CAR-T cells have been less effective against solid cancers.
“An alternative is to use an ‘off the shelf’ treatment made from healthy donor immune cells, but in order to do this care must be taken to avoid graft-versus-host disease, where the donor immune cells attack the patient’s body.
“The Fisher Lab discovered a way of engineering the previously under-utilised gdT cells, which have been clinically proven to be safe when made from unrelated donor blood. This offers a more cost-effective alternative to current per-patient manufacturing.”
As a component of the trial, researchers administered several treatments to the mice: unmodified gdT cells, an anti-tumor antibody, OPS-gdT cells combined with a bone-sensitizing drug, and CAR T-cells.
They discovered that the combination of OPS-gdT cells with the bone-sensitizing drug was the most effective. This drug, previously used to strengthen weak bones in cancer patients, successfully prevented tumor growth in the treated mice, keeping them healthy three months post-treatment.
Dr. Fisher highlighted that fact that thousands upon thousands of people suffer from cancer that spreads to the bones, with very few curative options available. He further emphasized that this study represents an exciting step towards developing a possible new treatment.
“Our hope is that not only will this treatment work for osteosarcoma but also other adult cancers.”
After the successful preclinical trial results, the team is now gathering data on the effectiveness of OPS-gdT cells in treating secondary bone cancers. They aim to advance to an early-phase clinical trial involving patients with secondary cancers within the next 2 years.
This work received the backing from UCLB, the innovation commercialization arm of UCL. Sara Garcia Gomez, Senior Business Manager at UCLB, indicated that they work closely with leading clinicians to help bring new treatments from the lab to patients, with limited treatment options available for bone cancers, this study has shown promising potential for new therapies. She added that they will continue to collaborate closely with Dr. Fisher and his team through the next critical stages of exploring this new approach.
The research also received the backing from the UCL Technology Fund and the National Institute for Health and Care Research GOSH Biomedical Research Centre (NIHR GOSH BRC). Additionally, it was supported by Professor Katia Scotlandi from the Rizzoli Orthopaedic Institute in Bologna, the Children’s Cancer and Leukaemia Group, as well as the Little Princess Trust.
As the cancer rates grow, with the victims becoming younger and younger many scientists have called for the need to increase the focus on the possible causes such as diet and lifestyle and need for more treatments.
