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Prelude Seed Grants fund real cancer research

Raising money for research. That’s the Prelude to a Cure mission. We’re proud to share some of the resesults of the research we’ve funded, as well as some of the ongoing studies made possible by the generous supporters of Prelude to a Cure.

We invite you to learn more about how you can participate.

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Dr. Ben Creelan

Dr. Ben Creelan: Dr. Creelan earned his bachelor’s degree in chemistry at Willamette University. He graduated from medical school and residency at Jefferson Medical College in Philadelphia, followed by oncology fellowship at USF. Creelan is currently an Associate Member in the Thoracic Oncology Department at Moffitt and holds a courtesy appointment as Assistant Professor at USF. He is active nationally in clinical trials using adoptive cell transfer, which use patient’s own live immune cells to fight their cancer.

Theory: The goal of this project is to create a more advanced platform to identify and validate neoantigen-specific T cells, identify the patient-specific antigens which appear to be attracting the T cells and driving the responses.

Summary: Neoantigens are foreign proteins which are created when cancer cells mutate. It is an important mystery why cancer patients can have T cells which recognize these neoantigens, and yet fail to eliminate the abnormal cell. The premise of this research is to devise a high-throughput screening method to identify effective neoantigens within a tumor, so that our immune system can be re-directed to destroy these cells forever. He expects this will lead to more durable remission in lung cancer patients. The short-term impact would be the ability to manufacture neoantigen peptide vaccines for use with checkpoint inhibitors, screen tumor infiltrating lymphocytes (TIL) cultures for neoantigen-specific fragments and could provide a tool to understand the mechanisms of immunotherapy resistance. Additionally, with the research assistance of Dr. Wang, a collaborative paper is scheduled to be presented at an upcoming EGFR Resisters Summit. This research has wide reaching implications for better treatment options.

Mass Spectrometry Analysis of Immune Checkpoint Proteins in Lung Cancer

Dr. Teresa Boyle

Dr. Teresa Boyle: With the results of the preliminary research, Dr. Boyle obtained extramural funding from the FL Bankhead Coley grant as well as philanthropic funding from the Salah Foundation to continue to pursue utilizing mass spectrometry panel test in lung cancer specimens collected through the rapid tissue donation program. Dr. Boyle’s plan is to use this panel development to identify overexpressed biomarkers that will help more patients. Dr. Boyle graduated from Harvard University College of Medicine, her residency at University of Colorado in Clinical and Anatomic Pathology and a Fellowship from Stanford University in Molecular Genetic Pathology. She was the second recipient of the Barbara Bauer Innovative Research Grant Program at Moffitt Cancer Center.

Theory: To develop mass spectrometry methods to detect multiple proteins that may influence immunotherapy outcomes.

Summary: Lung cancer specimens are often limited in quantity so the is great need to develop methods that can analyze many proteins at one time in a single small sample. A liquid chromatography-multiple reaction monitoring mass spectrometry assay (LC-MRM) was developed in order to measure expression for more than 38 different proteins in a single experiment. This was applied to lung cancer cell lines and Formalin-Fixed Paraffin-Embedded (FFPE) lung tumor tissues which were analyzed to determine the expression levels of the target proteins in kinase inhibitors and immune checkpoint inhibitors.

Evaluating Combined aPD-1 Immunotherapy and Radiation Therapy in a Preclinical Mouse Model of Pneumonitis and Fibrosis

Dr. Bradford Perez

Dr. Perez: The grant awarded to him by Prelude led to 2 career Development Awards from the National Cancer Institute and support for 2 investigator initiated clinical trials. The initial work was published in the Journal of Thoracic Disease.

Theory: To evaluate whether combined aPD-1 immunotherapy in conjunction with Radiation Therapy increases the risk of pneumonitis compared to Radiation Therapy alone.

Summary: A current standard of care for Non-Small Cell Lung Cancer (NSCLC) is a combination of chemotherapy and radiation therapy. The purpose of this study was to see if treating these patients with anti-PD1 immunotherapy in conjunction with radiation therapy was safe and might offer an opportunity to improve patient outcomes. A side-effect of both radiation and immunotherapy can be pneumonitis which is a non-infectious cause of lung inflammation and fibrosis. Lung fibrosis is a thickening or scarring of the tissue which is normally thin with lacy walls of the air sacs in the lungs. Dr. Perez tested if using a combination of radiation and anti-PD1 therapy would increase toxicities such as lung fibrosis which can be life-threatening. This project did not demonstrate significant increased risk with anti-PD1 and thoracic radiation therapy, although some changes were noted upon evaluating the lungs of mice that received radiation with anti-PD1 immunotherapy vs anti-PD1 immunotherapy alone.