My experience in the Fred Hutch Explorers Program has been invaluable, expanding my scientific knowledge and exciting me about research topics as unexpectedly complex as protein folding to bioethics. Moreover, it has given me a much deeper understanding of the properties of cancer and the cutting-edge immunotherapies being developed to treat patients.
A specific highlight was a particularly fascinating presentation by Alicia Morales, an educator and researcher with Fred Hutch, on immunology and cancer fighting immunotherapies. One such therapy is CAR T-cell therapy. This harnesses the power of a patient’s own T-cells, which are a type of white blood cell that can recognize and kill cancer cells. The patient’s T-cells are extracted and a specialized virus is used to deliver the genetic instruction for expressing CAR (chimeric antigen receptor) by the cells. This synthetic molecule gives the patient’s T-cells the ability to recognize and kill cells with a particular marker, the surface protein CD19. Cancerous B-cells, another type of blood cell, can try to evade the immune system with mutations that give them these CD19 surface proteins instead of the abnormal surface proteins that T-cells usually use to recognize cancerous cells. The engineered CAR T-cells are able to recognize and kill cells with CD19, meaning cancerous B-cells are no longer able to hide. CAR T-cell therapy can be used to treat cancers that involve these mutated B-cells, like Acute Lymphoblastic Leukemia (ALL). After the CAR T-cells have been engineered, they are multiplied and infused back into the patient.
The above image shows the steps involved in completing CAR T-cell Therapy, as outlined in the preceding paragraph.
Image from Biorender.com
As exciting as the science behind CAR T-cell therapy is, what’s more thrilling is the impact it has had on real patients who’ve received the therapy in clinical trials. One such patient is Kristin Kleinhofer, diagnosed with ALL in 2010. Two years of chemotherapy resulted in only a year and a half of remission, followed by participation in a clinical trial of an experimental chemotherapy and a blocked stem cell transplant. In 2014, she enrolled in the Fred Hutch CAR T-cell clinical trial and would be among the 93% of participants who went into remission after receiving the treatment. While more work is required to further improve the therapy, its concrete impact on the lives of cancer patients like Kristin shows great promise.
This program also introduced me to other outstanding research being done at the Fred Hutch. One specific project is looking into how inducing short-lived changes in mRNA could improve the effectiveness of some immunotherapy drugs. This research is being co-led by Fred Hutch computational biologist Dr. Robert Bradley and Memorial Sloan Kettering Cancer Center oncologist Dr. Omar Abdel-Wahab. Their goal is to make tumor cells more easily recognized by the body’s immune cells. By using drugs that disrupt the mRNA production process, such as indisulam or MS023, they can trigger errors that cause tumor cells to sprout neoantigens, which are new and varied surface proteins. The immune system would use these neoantigens to recognize the tumor cells as foreign and start to attack the cancerous cells. Unlike mutagens that permanently damage cellular DNA, the altered mRNA does not linger for very long in the body. While this research is still in its early stages, it is another example of how scientists are developing new ways to harness the body’s own immune system to fight cancer. This research is important because it offers a different approach to fighting cancers that are not responsive to checkpoint blockade immunotherapy drugs that are currently used.
I am very grateful that I was able to participate in the Fred Hutch Explorers Program and learn about the many fascinating advances in cancer research being made by a united community of scientists and innovators.
Sources:
Keown, Susan. “93 percent of advanced leukemia patients in remission after immunotherapy.” Fred Hutch, 25 April 2016, 93 percent of advanced leukemia patients in remission after immunotherapy (fredhutch.org). Accessed 25 August 2021.
Russell, Sabin. “How RNA-altering drugs might improve anticancer immunotherapies.” Fred Hutch, 24 June 2021,How RNA-altering drugs might improve anticancer immunotherapies (fredhutch.org). Accessed 26 August 2021.