Dr Jun Ishihara, Dr Koichi Sasaki, and Dr Akinobu Hamada 

Imperial College London

Jointly funded project with BCRT (2024-2027)

BACKGROUND TO THE RESEARCH PROJECT

Despite optimal management of localised osteosarcoma disease, over 50% of patients develop metastatic disease or recurrence, which lead to poor survival outcomes in approximately 19 months.  Immunotherapies, activating immune cells to attack cancers, became standard therapy in many other cancer types and enabled prolonged effects including prevention of recurrence and metastasis. However, osteosarcoma responds poorly to current standard immunotherapies due to A) inactivation of the immune system, B) resistance to immunotherapy, and C) difficulty in locally delivering drugs to tumour sites. Immunotherapies can achieve long-term effects including prevention of metastasis and recurrence. There remains huge room for improvement for immunotherapy in osteosarcoma as many patients suffer due to lack of treatment options and recurrence/metastasis.  

PRELIMINARY DATA

This project is starting soon and marks the first project that Willberry has co-funded with BCRT!

Preliminary data from the Ishihara lab has produced a promising immunotherapy protein called interleukin-12 (IL-12) that is known to successfully activate anti-tumour immune cells against several cancers. Despite its strong antitumour activity, IL-12 induces severe systemic toxicity in its native form. The lab found that several cancers including osteosarcoma increase collagen expression compared to normal tissue. They successfully reduced its toxicity, by attaching a collagen-binding domain (CBD), which enables tumour-specific delivery of IL-12. 

The team hypothesises that this newly developed tumour-specific bioengineered immunotherapy (CBD-IL-12) can become a breakthrough for osteosarcoma, especially against recurrent metastatic osteosarcoma.