Several immune checkpoints regulate the function of immune T cells and help tumors evade immune destruction. Approved immune checkpoint inhibitors are large, protein antibodies. These antibody therapies possess several inherent shortcomings such as lack of oral bioavailability, limited tumor tissue infiltration, and possibility of adverse immune reaction because of significantly longer retention time in the body.
Dr. Sachin Patil is investigating the interaction between two specific proteins expressed on the surfaces of immune T cells and cancer cells. The pathological interaction between these two proteins has been shown to act as an “off-switch” that prevents the immune T cells from recognizing and attacking cancer cells. He wants to know (a) if these proteins present any “druggable” pocket at their interface, and (b) whether he can target them successfully by identifying small-molecule inhibitors, using novel, integrated molecular screening approach.
His work involves potential discovery of novel drug and drug-like molecules that inhibit a pathological protein-protein interaction associated with cancer. This particular protein-protein interaction under study has a very large binding interface that has proven to be challenging to target using small-molecule compounds. He is utilizing for the first time a systematic scientific effort involving integrated virtual and experimental screening approaches to discover drug and drug-like compounds against this traditionally challenging, protein-protein interaction target. The screening approach, if successful, may also prove useful in investigating other such protein-protein interactions. This work, supported by the Smith Trust, may have broader, extrinsic scientific merit beyond the primary focus of cancer immunotherapy field.
Sachin P. Patil, Ph.D., Widener University. The main aim of the Patil Laboratory at Widener University is to identify non-peptidic, small-molecule immune checkpoint inhibitors that have potential to overcome all of the limitations associated with the larger protein antibody therapies. W. W. Smith Charitable Trust Research Project: “Identifying Small-Molecule Immune Checkpoint Inhibitors for Cancer”