SU2C-Lustgarten Foundation-SITC Pancreatic Cancer Convergence Research Team
Computational Deconstruction of Neoantigen-TCR Degeneracy for Cancer Immunotherapy
The team is building on the work started under a Convergence 1.0 grant but further explore the underpinnings that constitute pancreatic survivorship. By looking at few individuals who survive pancreatic cancer for long periods of time, the team identified an initial set of high-quality neoantigens, or protein tags, on cancer cells that the immune system recognizes. This project will continue the work to understand what makes a high-quality neoantigen and how the microbiome influences how the immune system recognizes it, with the goal of developing a method for creating vaccines to treat pancreatic cancers. This research will have a significant impact on understanding neoantigen-T cell immunobiology and could improve the treatment prospects of pancreatic cancer patients. This Convergence Research Team will work in collaboration with Microsoft Research, utilizing Artificial Intelligence (AI) and machine learning.
SU2C-Lustgarten Foundation Pancreatic Cancer Interception Team
Developing Novel Approaches to Detect and Treat Early Pancreatic Cancer
November 2017 – October 2021
This Interception Research Team is evaluating unique and new approaches in combination with radiation therapy and surgery. The team is utilizing SU2C’s unique “tumor organoid” technology in which an individual patient’s tumor cells are grown in the laboratory, creating “mini tumors” which can then be tested to see if a particular treatment is optimal. The team is also studying changes in the tumor microenvironment – the cells that support cancerous cells in a tumor – to see if there are changes and the environment is more or less “inhabitable” following treatment.
SU2C-Lustgarten Foundation Pancreatic Cancer Interception Dream Team
Intercepting Pancreatic Cancer in High-Risk Cohorts
November 2017 – October 2021
This Interception Dream Team seeks to develop a screening test using machine learning techniques to identify and diagnose pancreatic lesions currently not detectable with existing technology. This Dream Team also seeks to develop a first-in-human vaccine to prevent or stop development of PDAC in individuals with an inherited predisposition, who have evidence of precancerous changes in their pancreas and mutant KRAS gene in endoscopic pancreatic juice samples. To further enhance earliest possible diagnosis, this Dream Team plans to create a blood test for identifying individuals at risk for PDAC who would be candidates for early detection using imaging technology.
SU2C Catalyst® Research Grant–Merck Supported Project
Targeting VDR to Make Pancreatic Cancer Competent for Immunotherapy
May 2017 – April 2020
Immunotherapies have shown benefits across a range of human cancers, but so far have not worked well in pancreatic cancer patients. Recent evidence suggests that one major roadblock for the effective use of immunotherapies in pancreatic cancer patients is that the tumors are effectively hidden, preventing the immune system from recognizing and killing them. Research from this team suggests that therapies targeting the vitamin D receptor will perhaps “unmask” the pancreatic tumors and allow the immune cells to reach them, creating the possibility that immunotherapies will be effective.
The goal is to test if targeting the vitamin D receptor will unlock the potential of immunotherapies to kill pancreatic cancer tumor cells and potentially establish a therapeutic combination for controlling advanced pancreatic cancer, extending patient survival, and reducing patient side effects. Additionally, this team hopes to identify features that drive patient responses to immunotherapy and gain insight into additional strategies for converting immunotherapy resistant tumors into tumors that respond to treatment.
SU2C-Lustgarten Foundation Translational Research Team
Chimeric Antigen Receptor T Cell (CAR T) Therapy for Pancreatic Cancer
April 2017 – March 2018
This Research Team is studying CAR T cell immunotherapy in metastatic pancreatic cancer patients, looking for changes in DNA “on and off switches” (epigenetic changes) following treatment with CAR T. The team ultimately seeks to identify epigenetic changes for better understanding of why certain patients respond to treatment compared to non-responders.
SU2C-Cancer Research UK-Lustgarten Foundation Pancreatic Cancer Dream Team
Reprogramming of Transcriptional Circuitry to Control Pancreatic Cancer
January 2016 – December 2018
This Dream Team is continuing the work started on the original SU2C Pancreatic Cancer Dream Team, which found that vitamin D receptor plays an important role in determining pancreatic cancer susceptibility to chemotherapeutic agents. This Team is studying vitamin D receptors to determine if it is an effective “super-enhancer” which improves patient response to chemotherapy.
SU2C-National Science Foundation-Lustgarten Foundation Convergence Research Team
Liberating T Cell Mediated Immunity to Pancreatic Cancer
September 2015 – August 2019
The Research Team’s long-term goal is to understand the factors that lead to resistance or response in patients treated with various forms of cancer immunotherapy. In particular, the goals are to investigate patient epigenetic variation that influences the response to immunotherapy and to use epigenetic therapeutics alone or in combination with immunotherapy to inhibit tumor progression as well as to overcome resistance to immunotherapy.
The team will identify genetic and epigenetic features in CAR T cells and/or cancer cells that will help predict which patients will respond to the immunotherapy, with an eventual goal of initiating clinical trials that employ a combination of approaches to therapy. This will create strong synergy for a unified, multidimensional project aimed at generating more effective CAR T cells therapy for pancreatic cancer patients, with potential broad implications for immunotherapy directed toward other cancers.
SU2C-Lustgarten Foundation Pancreatic Cancer Dream Team
Transforming Pancreatic Research to Treatable Disease
July 2014 – June 2017
This Dream Team has been investigating combinations of treatments, focused on different and unique pathways involved in immune response to treatment found in the tumor and the “stroma” or the supportive environment that sustains cancer cells in tumors. This team has achieved durable responses to treatment, with a treatment vaccine they developed.
SU2C Pancreatic Dream Team
Cutting off the Fuel Supply: A New Approach to the Treatment of Pancreatic Cancer
December 2009 – May 2015
This Dream Team evaluated combinations of treatments, seeking better patient outcomes. The Dream Team’s work led to the first approval for a new pancreatic cancer drug in 30 years. The FDA approved a new combination of drugs that enables longer survival in patients with advanced pancreatic cancer on September 6th, 2013. Pancreatic cancers are scavengers, after “eating” sugars it eats proteins to sustain itself. This drug creates a Trojan horse for the cancer to feed on and it eventually dies. This Dream Team also developed a new method of identifying pancreatic tumors that have spread to the brain and liver, which could significantly aid in diagnosis.
The combination of Abraxane and Gemcitabine is now being explored for other types of cancers. This Dream Team was also able to identify that vitamin D receptor plays an important role in determining pancreatic cancer susceptibility to chemotherapeutic agents, under continued investigation by the SU2C-Cancer Research UK-Lustgarten Dream Team.