These past 2 weeks, I had the most amazing experience being a part of the Fred Hutch Explorers program! We touched on virology, CRISPER, bioethics, protein folding, and of course, our case study on cancer and immunotherapies. We also got some hands-on lab work (even from home!) and had many incredible speakers from the Hutch.
The guest speaker that stood out to me the most was Dr. Eric Nealy, who gave a talk on his PHD research project getting white blood cells to attack Pediatric Brain Tumors (PBTs). These are the exact 3 fields I can see myself pursuing in the future: pediatrics, neurology, and oncology, which was the first reason I was so captivated. His project virtually created a mouse trap, or a “roach motel”, as he called it, for PBTs as a post-surgery “clean-up”. The need for this comes from the conundrum when removing cancer from the brain and not wanting to cut too much brain matter out and causing brain damage, but not wanting to leave cancer cells behind to continue to grow. To explain the project a little more, Dr. Nealy used a lure/bait in the form of chemokines, an immunotherapy “poison”, and a hydrogel carrier that could be injected in a specific site. This simple idea applied to something as complex as cancer was a form of creativity that really inspired me.
When immunotherapy was injected without the entire trap, it was found that the radius of its effect was very limited. This was why Dr. Nealy needed to bring the cancer closer to the body’s killing mechanisms. Chemokines are a natural chemical that is a stimulus for chemotaxis, or how cells move throughout the body. They are specifically thought to be how cancer moves both locally and to other organs. By injecting chemokines, the cancer will flock towards the area, which is when the t-cells and antigens’ limited radius can be effective. This project took an interdisciplinary approach, combining cell biology (chemokines), immunology (how the cancer is being killed), and chemical engineering (the hydrogel vehicle). It taught me that for even one project, it is very useful to collaborate and learn about multiple trades and fields. It also taught me that I do not just have to choose one of the fields I am interested in, but I can apply and learn about all of them, giving me hope and goals for the future.
Another exciting project we got to learn about at the Explorers program was a treatment for advanced leukemia that put 93% of patients in remission: immunotherapy. This was the case study I had mentioned earlier – a patient named Kristin Kleinhofer who was a part of the clinical trial for a CAR-T cell treatment.
Take a look at the timeline of her illness and what it looked like on a cellular level:
What happened was that Kristin was diagnosed with B-cell acute lymphocytic leukemia in 2010, and after chemotherapy and treatment the first time, Kristin went into remission for a year and a half. Then, her cancer mutated to resist chemotherapy and evade her immune system, and thus began her relapse. Before coming to the Hutch, Kristin went to Stanford for some experimental chemotherapy treatments. This is usually coupled with a bone marrow transplant to replenish the immune system, but when her transplant donor fell through, Kristin needed another option. Fred Hutch had an extremely early-phase clinical trial that took immune cells from a patient’s own body, and genetically engineered these T-cells to add Chimeric Antigen Receptors (CAR-T cells) that would recognize her cancer cells. Cancer evades the immune system by presenting CD19 proteins that usually are there to reassure the immune system they are normal cells, and not to kill them. By modifying a T-cell to recognize CD19 as cancerous, then reproducing these T-cells in a larger amount and re-transfusing them back into her body, her immune system was able to kill all the B-cells with CD19, including cancer cells. This treatment, unexpectedly, worked! She got a stem-cell blood transfusion to replenish the killed B-cells, Kristin’s own body was able to fight the cancer, and in 2014 she was back in remission. This therapy is now FDA approved for her type of cancer, and is helping many patients.
Before learning about immunotherapy, I was not sure what exactly I wanted to do research on in the future. But now, I really want to be a part of this type of research for future patients of all different types of cancers. Cancer is important to me because of how many people around me have been affected, and the idea that one’s own body will be able to fight back against the cancer gives me so much hope for the future.
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