T-Cell Trafficking into the Cold Tumor Immune Microenvironment
Abstract
FY 18 PRCRP Topic areas: (1) Cancer Immunotherapy (2) Cancers of children, adolescents, and young adults Scientific Objective: My lab is interested in two cancers that frequently affect children and young adults called synovial sarcoma and myxoid/round cell liposarcoma. Although these diseases are rare, when they strike it is devastating for the patients and their families. The few treatment options we have for patients in an advanced stage only work for a short while and are extremely toxic. However, these two cancers are unique in that they both almost always strongly express a good target for immunotherapy called NY-ESO-1. We have used genetically modified T cells and vaccines to target NY-ESO-1 and try to eliminate these cancers. However, while these treatments work for a time, responses are rarely complete or durable. We have been trying to understand how these cancers escape our immunotherapies even though they have excellent expression of our target. We believe that the T cells that should be killing these cancers are not penetrating into the tumors well, and when they do, they are not functioning as well as they should. It has been difficult to test ways to make these T cells work better, because our T cells and the target are both human and not modeled well in mice. In order to overcome this challenge, we have been developing a new kind of model system called an organoid. This artificial tumor uses all human tissues and has an artificial vessel (called a microfluidic channel) that the immune cells can travel through. In this project, we will use the organoid model to test ways to make our tumor-targeted T cells enter tumors and work better once they are there. Applicability of the Research: We are focused on two specific rare cancers because they have such good, well-characterized targets for immunotherapy and because of this we sometimes call them model diseases. However, the lessons we learn through this project will be widely applicable. We estimate that 20% to 30% of all cancers evade immune recognition in a similar pattern to these cancers, and by overcoming immune escape in these two model cancers, we will be able to overcome immune escape in the many similar tumor types. FY18 Military Relevance Focus Areas: (1) Sarcomas are thought to be related to Veterans exposure to Agent Orange or other herbicides during military Service, one of the FY18 Military Relevance Focus Areas. (2) Successful immunotherapies have the potential to address significant gaps in cancer treatment within the U.S. population, including military Service members and their beneficiaries, and perhaps especially Veterans, another FY18 Focus Area.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910582
Entities
People
- Seth M Pollack
Organizations
- Fred Hutchinson Cancer Center
- United States Army