Abdullah Farooq - Three Minute Thesis - 4/25/2023

this is Emily Whitehead ten years ago Emily received an experimental immunotherapy for the treatment of an aggressive and rare form of leukemia amazingly 10 years later she still completely cancer-free we're at a moment now where thanks to immunotherapy Curative treatments for cancer are possible immunotherapy involves harnessing our own immune system and retargeting it to kill cancer cells however if Emily had been diagnosed with a solid

tumor like pancreatic cancer or lung cancer her prognosis might have looked significantly different that's because in solid tumors we have to deal with an immunosuppressive tumor microenvironment as you can see in the bottom left corner a cold tumor is one that excludes immune cells and in which an inflammatory anti-tumor response is very difficult to mount on the other hand a hot tumor is one in which

immune cells are able to enter into the tumor and actually mount an inflammatory response so in order to make immunotherapy more conducive to an actual therapeutic context we want to be able to convert cold tumors into hot tumors and to do that we can take advantage of the natural language that immune cells use to communicate with each other called cytokines these are small soluble proteins that

can either ramp up or damp down the immune system however pro-inflammatory cytokines can be extremely toxic when injected systemically into a patient and have actually caused fatalities in clinical trials my work harnesses the spatial Precision of focused Ultrasound with genetic circuits that enable uh the harnessing of that uh focused ultrasound to induce a biological response so using focused ultrasound has a high degree of spatial resolution

and we can Target a two millimeter regen additionally with focused ultrasound we can induce hyperthermia which actually induces a local elevation in temperature that elevation in temperature doesn't actually destroy the tumor but it acts as a switch just like in electronics and it catalyzes a DNA inversion after that DNA inversion a pro-inflammatory cytokine in my case called il-12 is able to potently stimulate T cells we're

currently working on testing this in mice and our goal is to be able to create a system in which we can inject engineered cells into a patient and then the user physician will be able to selectively Define where and when an immune response is going to be mounted our goal is to make sure that cases like Emily's can be realities for patients with cancer no matter

what their type is thank you