Collaboration has always been at the core of what we do at the Flint Animal Cancer Center, and we’re proud to have worked with the CU Cancer Center for more than 40 years. Together, we make up Colorado’s Cancer Center. And together, we’re collaborating to conquer cancer including by partnering on cutting-edge pediatric osteosarcoma research.
Dr. Regan DVM, PhD, of the Flint Animal Cancer Center, and Dr. Michael Leibowitz, MD, PhD, of CU, were recently awarded an $800,000 grant from the V Foundation to further their collaborative pediatric osteosarcoma research project. The V Foundation was co-founded by ESPN and legendary basketball coach Jim Valvano. Their mission is to fund game-changing research and all-star scientists to accelerate Victory Over Cancer® and save lives.
Drs. Regan and Leibowitz will use the funding to test a combination of oral immunotherapy drugs with CAR T cells in dogs with metastatic osteosarcoma to predict its efficacy in humans with osteosarcoma. The hope is that this research will lead to ways to prevent or treat the spread of the disease to the lungs.
For many patients with metastatic osteosarcoma, surgery is simply not an option, and existing drugs are either ineffective or associated with significant side effects. In these cases, the prognosis is very poor. There have been no real advances in the treatment options and outcomes for these patients in over 40 years. This team is focused on providing safer, more effective treatments.
Dr. Regan has previously identified a two-drug combination – both of which are already FDA-approved – for metastatic osteosarcoma. This combination shows great promise in slowing the growth of this type of cancer. When taken together, these drugs target a type of immune cell called a macrophage. These cells are used in the growth and spread of tumors. By effectively blocking these cells with this drug combination, the spread of the cancer is greatly reduced. The drugs, which include a blood pressure drug, losartan, and the anti-cancer drug sunitinib, are now in a human osteosarcoma clinical trial at Children’s Hospital Colorado in Aurora.
In the initial trial of the losartan-sunitinib combination in dogs at the FACC, Dr. Regan was able to achieve longer-term disease stabilization in 50% of patients. Another 25% saw a regression in tumors.
These results are promising but the team is looking for ways to build on these results. The next phase of this pediatric osteosarcoma research is funded by the V Foundation and many other entities. Drs. Regan and Leibowitz will build on the existing two-drug combination to see if results can be improved with a third addition. The new study will include adding CAR T-cell therapy to the protocol.
The chimeric antigen receptor (CAR) T cells are engineered to seek out and destroy cancer cells. They will specifically target a group of cells known as fibroblasts. These cancer-associated cells are a part of the tumor environment; they work to recruit the macrophages to work for the cancer cells.
The theory is that by adding this additional level of anti-tumor agents to the mixture, metastatic growth will be slowed further.
This study will take four years to complete. At the Flint Animal Cancer Center, dogs with naturally occurring osteosarcoma will be given a combination of losartan, sunitinib, and the CAR T cells developed by Dr. Leibowitz and his lab.
“The major benefit of this comparative oncology approach is that we can jump ahead a little bit,” Dr. Regan said. “We can test things in dogs that you might not necessarily jump right into a human clinical trial. Dogs also have a shorter lifespan than humans, so their progression of cancer is much more accelerated. You know if things are working or not working much more quickly.”
We’re hopeful for the results of this study and note that none of this could be done without our supporters. With the help of the V Foundation and many others, this pediatric osteosarcoma research could change the lives of patients in the future.