Cancer/T-cell research/Novel therapies
University of Colorado Anschutz Medical Campus
Our long-term goals are to develop novel approaches for treating immunorefractory cancers and to develop predictive models and diagnostics to identify compounds that sensitize tumors to T cell-based therapies.
One of our goals is to develop and test the antitumor efficacy of novel ‘universal’ co-receptors that lower the activation threshold of NK, CD4, CD8 T cells towards weakly immunogenic and/or lowly expressed antigens. Our published and ongoing studies indicate an ability to restore and/or invigorate T cell responses against a variety of antigens including neoantigens as well as numerous cancer and viral antigens using novel synthetic immune cell receptors. A second focus under this aim is to elucidate the mechanisms by which tumor-reactive T cells undergo exhaustion and develop novel gene-based methods to reverse or prevent T cell exhaustion. A third aim under this goal is develop innovative strategies to selectively expand tumor-reactive T cells after transfer into patients.
A second goal in our laboratory is to determine the role that dysregulated inflammatory signals in cancer contributes to T cell suppression and develop therapies to mitigate these signals to restore immunity. We have identified and are currently testing several agents that restrain chronic inflammation for the purpose of restoring T cell immunity. As an extension of this goal, we are also developing predictive modeling of compounds that increase the efficacy of T cell therapies while reducing immune-related adverse events. We do so by integrating patient-specific data with advanced high throughput flow cytomtery-based cell characterization, genomic bioinformatics, and validation in preclinical studies. Working with key faculty from the University of Colorado, leaders in large-scale data sets and complex computational analyses, we are poised to develop and validate models to forecast which drugs could be used to ‘immunosensitize’ different cancer types.