William K. Decker, PhD, Associate Professor, Baylor College of Medicine
2016 Pittsburgh Cure Sarcoma Co-Founder Carl Firetto Memorial Research Award : “Outbred Canine Model of Adjuvant Immunotherapy for Angiosarcoma”
PLEASE DESCRIBE THE FOCUS OF THE RESEARCH PERFORMED IN YOUR LAB.
We study the basic immunobiology of dendritic cells and the manner by which this critical cell subtype orchestrates TH polarization. TH polarization sounds complicated – and it is – but can be explained relatively easily. The adaptive immune system makes two main types of fundamentally different immune responses. One of these responses, termed TH2, is aimed at eliminating pathogens that live outside of cells. These include most bacteria, yeast, fungi, and many parasites. The other type of response, termed TH1, is aimed at eliminating pathogens that live inside of cells. These include viruses and certain bacteria and parasites that reproduce in this specialized way. Since the TH1 immune response is very well-correlated with good outcomes in cancer, new knowledge in this area has substantial applicability to improved treatment paradigms in cancer immunotherapy. In addition to studying basic dendritic cell biology, we are always trying to translate what we learn in the lab toward the synthesis of better immune-based cancer treatments.
WHAT HAS INSPIRED YOU TO RESEARCH SARCOMA?
I have long had an interest in cardiac angiosarcoma because it is such a devastating disease and because so few treatment options are available for it. Here in Houston, Michael Reardon and Denton Cooley at the Texas Heart Institute pioneered the technique of cardiac autotransplantation for treatment of this disease. Unfortunately though this technique can extend life, it does not generate durable cure. I’ve always been interested in working on tough problems, and this one – though rare – is very tough. The disease is a virtual death sentence.
PLEASE SHARE A BIT ABOUT THE PROJECT THAT WAS FUNDED BY YOUR SFA RESEARCH GRANT AWARD.
I like dogs a lot, and angiosarcoma is also a devastating disease in dogs. The presentation is different – it most frequently presents in the spleen in dogs – but the results are just as devastating. Once a relapsed tumor reaches any size of significance, it bleeds and the animal dies of hypovolemic shock. Median survival is only 48 days after splenectomy, and unlike humans, it’s not a rare disease. This disease kills up to 1% of all dogs. So…given my affinity for dogs, my affinity for cancer immunotherapy, my affinity for angiosarcoma, and the fact that there is no existing mouse model of angiosarcoma that can be used to model immunotherapy, this seemed like a really great project for us. We took on an exceptionally devastating malignancy and applied a dendritic cell-based immunotherapeutic technique to its treatment. We were able to approximate almost precisely what we would have done in a human patient, and the results were very encouraging. We worked closely with teams of veterinary surgeons, oncologists, and pathologists as well as with many helpful pet owners to arrive at a clinical veterinary protocol that could be carried out by everyone involved. In both the per-protocol (5 animals) and the intent-to-treat (8 animals) group, median survival was doubled (109 and 105 days, respectively). Most importantly, one of the five animals in the per-protocol group, exhibited demonstrable remission of relapsed disease and died of old age still cancer-free. We were very encouraged by the exciting results and hope to move this strategy to the clinic in the coming years. We feel like we are making great progress against a really tough disease.
HOW HAS FUNDING FROM THE SARCOMA FOUNDATION OF AMERICA HELPED IN YOUR RESEARCH EFFORTS?
The Carl Firetto Memorial Research Award provided by the Sarcoma Foundation of America was critical to the implementation of this project, providing over 80% of the required funds. This project was on the drawing board for a long time, and SFA finally made it happen!