We just need to keep knocking.

NY-ESO-1 or New York esophageal squamous cell carcinoma 1 is an antigen that is associated with many cancers, but is expressed with particular vigor in synovial sarcomas and myxoid/round cell liposarcoma. Both of these sarcomas typically occur in about 1,000 young Americans every year. Although they can arise anywhere, they most often arise in the limbs, and sadly, they typically lead to death within two years when discovered at an advanced stage. 

At the Fred Hutchinson Cancer Research Center (Seattle, Wash.), Seth Pollack, MD, and his team are targeting NY-ESO-1 with an innovative strategy – development of a first-ever combination of two types of separately genetically engineered T cells (CD4+ and CD8+) supported with precision radiation. 

“Traditional chemo and radiation therapies have little impact on these cancers in the long term and make patients miserable in the short term,” says Dr. Pollack. “I have no doubt that new gene therapies will become the solutions we need to fight cancer. They are already transforming the world of medicine. 

“Gene therapy has had a huge impact on halting the progress of leukemia and lymphoma, and now we’re exploring how to apply what we learned in that process to fight other cancers. Researchers around the world are really just beginning to scratch the surface. There are many barriers, but there is incredible potential. Every time we knock down one barrier, many people benefit. We just need to keep knocking.” 

With a grant from Alliance for Cancer Gene Therapy, Dr. Pollack is determined to produce more consistent, complete, and durable responses to T cell therapies for solid tumors, especially synovial sarcomas, and myxoid/round cell liposarcoma. 

Leading up to this phase of study, Dr. Pollack achieved several important foundational breakthroughs. The insight he gained into harnessing the potential of Interferon-γ was published in Cancer Immunology Research, and the lessons he learned about leveraging a modified, third-generation, nonreplicating, integration-deficient lentivirus-based vector to pursue NY-ESO-1 were published in Clinical Cancer Research. In addition, a comprehensive review article characterizing the sarcoma immune microenvironment, including synovial and myxoid liposarcoma, was published by Dr. Pollack and colleagues in Cancer; and another assessing more than 50 subtypes of soft tissue sarcoma was published in an American Society of Clinical Oncology educational book. 

“I am a scientist, but I also see sarcoma patients in the clinic. Honestly, it can be heartbreaking. These diseases are always devastating. Some of these sarcoma patients are young people just starting out their lives. Some have young kids at home who depend on them. Some are trying to fight cancer while balancing a job and other responsibilities. It’s really hard. 

“How great would it be if we could take patients like these who are suffering and likely to die, and give them new hope for life? I think gene therapy offers our best hope for real progress toward real cures. We just need to keep knocking.” 

This Alliance for Cancer Gene Therapy Research Fellow is funded in part by Wendy Walk.