Rewiring T cell fate and function to enhance cancer therapeutics
Source: Steve Gschmeissner/Science Photo Library/Getty Images
Mission
Engineered T cell therapies (e.g. CAR T cell therapy) have revolutionized the cancer immunotherapy landscape by demonstrating remarkable clinical responses. However, poor T cell persistence and T cell exhaustion limit efficacy in patients and are major barriers to progress for the treatment of solid tumors. The Weber Lab, located at the Children’s Hospital of Philadelphia in the University of Pennsylvania Perelman School of Medicine, is developing novel approaches to reprogram CAR T cells with enhanced fitness and antitumor potency and uncover molecular mechanisms that govern human T cell fate and function.
Our primary goal is to bring curative T cell therapies to cancer patients.
Scientific Approach
CAR T cells require an extra “boost” to ensure potent and durable responses in patients. We’ve demonstrated that CAR T cells can be engineered with enhanced fitness using approaches that reprogram the transcriptome and epigenome (Weber et al. Science 2021; Doan et al. Nature 2024). This work is foundational to our research program centered around endowing human CAR T cells with exhaustion resistance and improved durability. We aim to identify and modulate transcriptional and epigenetic processes that redirect human T cells towards more therapeutic cell states. Multiomics analyses on experimental and patient CAR T cells will enable us to link biological pathways to cell phenotype, function, and patient outcomes, thereby informing our T cell engineering efforts. Collectively, our work will uncover pathways that govern human CAR T cell antitutmor function and dysfunction, identify novel targets for therapeutic intervention, and inform broadly-applicable strategies that improve CAR T cell efficacy in cancer patients.
Our Funding
Interested in joining our multidisciplinary team?
Please reach out to Evan Weber directly at weberew[at]chop.edu