Funded by The Little Princess Trust and administered by CCLG
Lead investigator: Dr Jonathan Fisher, University College London
Award: £244,413.68
Awarded July 2021
Osteosarcoma bone cancer affects teenagers, around half of whom die within 5-years of diagnosis. Treatment involves toxic chemotherapy and life-altering surgery including limb amputation. Osteosarcoma often becomes chemotherapy resistant, so new approaches are needed. Immunotherapy, where immune cells that usually fight infection are modified to fight cancer, has potential, but hasn’t yet worked against osteosarcoma for two reasons:
- The modified immune cells can’t find the cancer
- The cancer produces chemicals which turn off immune cells, so even those which do find the cancer are ineffective or don’t survive.
We think we can solve these problems by modifying immune cells called “gamma-delta T-cells”. We know that these cells are really good at killing cancer cells and our plan is to modify them so that they can find the cancer more easily and survive when they get there. We will alter and test the cells in the following ways:
- Giving the cells the ability to home to (find) osteosarcoma. We will test this in a petri-dish and then in mice who have osteosarcoma in their legs. We will inject the immune cells to veins in the tails of the mice and use a special camera to track them as they hunt the cancer.
- Making the cells produce chemicals which keep them fit and healthy when they find the cancers. We will test this by mixing the cells with osteosarcoma grown in the lab, studying how the modification affects immune cell health and behaviour.
- We will combine the two modifications and test them in mice with osteosarcoma. We hope that with improved homing and fitness the cells will seek out the cancer, remain active, and fight the disease.
The lessons learned are not limited to osteosarcoma; we hope to apply them to other cancer types in the future.