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Harnessing Dipeptidyl Peptidase Inhibition for Cancer Immunotherapy

Daniel A. Bachovchin, PhD

Dr. Bachovchin is an assistant member in the Department of Chemical Biology at Memorial Sloan-Kettering Cancer Center in New York. His SU2C Innovative Research Grant project, awarded in 2017, is titled “Harnessing Dipeptidyl Peptidase Inhibition for Cancer Immunotherapy.”

Cancer immunotherapy, in which a patient’s own immune system is harnessed to destroy cancer cells, is a revolutionary new approach for combating cancer. However, many cancers are not yet amenable to immunotherapy. Even for cancers for which immunotherapies exist, only a fraction of patients responds to such treatments. Additional research is, therefore, needed to identify new treatment options that target novel and/or complementary mechanisms of action. One particularly intriguing yet poorly understood small molecule drug, called Val-boroPro, has been shown to be an immune-stimulating agent with striking anticancer activity. However, significant toxicity concerns have so far impeded further clinical advancement. The mechanistic basis of Val-boroPro’s toxicity, and whether this toxicity can be separated from its promising anticancer efficacy, is not yet known. Dr. Bachovchin will address this question by determining the mechanisms of action of the drug to understand both why it is effective and why it is toxic so that only the anticancer mechanism can be exploited in future drug design. Using such drugs, this proposal aims to identify novel mechanisms to stimulate the patient’s immune system to eradicate cancer cells. This approach is unique in that it is distinct from the vast majority of ongoing studies that are focused on modifying or optimizing currently available immunotherapies. If successful, the proposed strategies could be rapidly translated into the clinic, where it will represent an entirely new mechanism for activating the immune system to kill cancer.