Professor Rutgers University Bridgewater, New Jersey, United States
Immune checkpoint inhibitors (ICIs) are new targeted cancer medications that reactivate the human immune system to attack tumor cells. These medications have revolutionized the treatment of skin and lung cancer and hold great promise for other types of cancer. But like most cancer medications, ICIs do not come without side effects. In some patients, these medications over-activate immune cells leading to organ damage. In fact, five years after completing ICI chemotherapy, 20% of patients have long-lasting problems with their kidneys. With the expected increase in prescribing ICIs, we anticipate an even greater number of cancer patients experiencing persistent toxicities. Unfortunately, the current animal models (such as mice and rats) do not respond to ICIs due to a mismatch of immune systems. Our research team has demonstrated that chimeric mice with a humanized immune system and tumors can recapitulate the renal pathologies (namely, glomerulonephritis, interstitial nephritis, and vasculitis) as well as hepatic and lung toxicity associated with ICI therapy in patients. Using spatial proteomics and flow cytometry, we have demonstrated that an array of T cell populations comprise the infiltrates surrounding regions of pathology. Using differential profiling of cytokines, growth factors, chemokines, and other molecular targets has been performed in plasma and kidney tissue and used to prioritize potential mechanisms of renal toxicity. This presentation will discuss the utility of this animal model to evaluate immune-related adverse events of immunotherapies.
