Research
Unleashing the immune system to target cancer
Insights from preclinical models have fueled the rapid development and remarkable clinical success of new therapies designed to unleash the immune system to recognize and eliminate advanced malignancy. Where highly toxic and non-specific chemotherapeutics have failed, the unprecedented success of cancer immunotherapies is creating new hope for cancer patients. However, not all patients respond to current treatments. Some types of cancer, such as pancreatic cancer, are uniquely resistant to even the most aggressive therapies. Thus, the lab's goal is to uncover why the immune system fails to eradicate such deadly malignancies in order to develop safe and durable immune-based treatments for cancer patients. We use many technologies and approaches including gene editing of primary T cells with CRISPR/Cas9, cloning and expression and functional analyses of novel T cell receptors, adoptive cell therapy with genetically modified T cells and immune checkpoint blockade. T cells that recognize and respond to cancer are tracked in vivo using flow cytometry, multiparameter immunofluorescence, 2-photon intravital imaging and by single cell gene expression analysis.
Investigating mechanisms of a productive immune response to pancreatic cancer
High-resolution ultrasound of a pancreatic tumor mass in control (top row) or following immunotherapy (bottom row). By Adam Burrack.
2-photon imaging of pancreas tumor (red), genetically engineered T cells (green), extracellular matrix (blue) and cross-presenting dendritic cells (yellow). By Meagan Rollins.
Fold change in murine tumor radiance three weeks post immunotherapy. By Adam Burrack
Detection of tumor (neoantigen)-specific T cells in pancreatic cancer using fluorescently labeled MHC class I tetramers. Tetramer generation and staining by Adam Burrack.
Insertion and deletion analysis of gene-edited primary T cells using CRISPR/Cas9 . Gene editing and genomic analysis of primary T cells using Cas9RNP+gRNAs. By Jackson Raynor.
Dr. Meagan Rollin's imaging on the cover of JCI Insight Volume 7, Issue 7. 2-photon microscopy of type 1 dendritic cells infiltrating pancreatic cancer.
Pancreatic tumor cells (purple), CD8+ T cells (red), macrophages (pink) and the immune checkpoint molecules PD-1 (yellow) and PD-L1 (green) expression in human pancreatic cancer. These data suggest that some pancreatic cancers may contain tumor-specific T cells.
Cover of Cancer Immunology Research.
