Learning of Improving The Incredible Immune System
Learning and connecting with others has been particularly harder in the last few months, for our screens were the barrier. But, despite the unprecedented circumstances, I found both Alicia Morales’ lecture on the immune system along with immunotherapy to be notably stimulating because of how she delivered the content. Going into the Zoom meeting, I expected a bunch of dense content showcased along with sophisticated wording that I would not be able to understand, yet I understood and learned a lot about the incredible immune system and ways researchers are working on to better suit them to tackle cancer.
I had always known about the immune system as something to protect our bodies from invading pathogens, but I never dove into the specific functions that each portion of our immune system did in preventing diseases. I had always known of T-cells, but I had not known of the significant role they play within the immune system. T-cells are a part of the adaptive immune system that help fight off infections through recognizing “sick” cells and killing them. With this function of T-cells, scientists, like Alicia Morales, are able to work towards utilizing the T-cells to target cancer cells specifically, as potent cancer cells are still able to evade our robust T-cells. A few of these immunotherapies are namely the following: TILs, CAR T-cells, and Transgenic TCRs.
Alicia Morales’ Diagram of The Immune System
In this diagram, the pathway a virus, bacteria, or any other pathogen takes is depicted.
The graphic shows a pathogen entering through your skin and faces macrophages, natural killer cells, and dendritic cells that travel to the lymph node.
The lymph node then activates T-cells that either turns into a memory T-cell or undergoes apoptosis (programmed cell death)
These T-cells also activate B-cells that either turns into a memory B-cell or undergoes apoptosis as well
Newfound Target for Drugs: The “Frankengene”
In the Fred Hutch article “New study shows cancer-causing ‘Frankengene’ mutation could be a target for new drugs,” researchers from the Holland Lab found YAP, a growth-promoting gene, causes cancer when fused to other genes. In this study, the Holland Lab tested the impact of four different YAP gene fusions in mice brain cells and found that tumors developed in the presence of all four fusions. While looking side-by-side of all four of the YAP gene fusion results, researchers were able to find the key functions of YAP that trigger cancer and figure out how the gene fusions bypass typical molecular controls.
With the knowledge of how YAP gene fusions play a role into cancer, a market for new drugs could open up. Working on their understanding of how certain compounds acted upon YAP gene fusions, Dr. Taran Gujral—a systems biologist—and Dr. Frank Sulzewsky—a postdoctoral fellow—examined the experimental compounds that block YAP protein activity on the tumor cells with YAP gene fusions. The results were promising as the compounds slowed the growth of cancer cells in their lab dishes.
Another instance of where the team is heading in terms of anti-YAP drugs is their clinical trials with an experimental drug called verteporfin. Currently, the drug is being tested against breast cancer, but with the team’s findings, there is evidence to suggest that similar compounds would work on other tumors carrying YAP gene fusions, such as many ependymomas. This is especially significant being that only 60-65% of people with this type of cancer survive for at least five years. That statistic could drop, knowing that YAP gene fusions are found in 25-30% of ependymomas.
About The Holland Lab
The Holland lab at Fred Hutch addresses the molecular basis of brain tumors to develop new approaches to treatment. Their research is primarily focused on crafting mouse models of brain cancer that can mimic the behavior of diseases. Producing these mouse models has even led to clinical trials with glioma—which is a tumor that occurs in the brain and spinal cord—patients. Developing these mouse models is especially important in launching clinical trials on brain cancers because of the role animal models play in preclinical trials; the trial may be potentially detrimental to patients in the first phase of clinical trials if the treatment or drug is not tested on an accurate model.
In addition to working with mouse models, the team had also developed new techniques for imaging mice for preclinical trials. Proceeding with preclinical trials in mice, the team needs to identify a tumor along with its size and position over time. To identify these certain things, the team had used MRI scanning, just as MRIs are used in people, but MRIs only reveal anatomical structure, rather than biologic processes. To get around this issue, the team utilized bioluminescence imaging strategies that allows them to identify mice with tumors and to non-invasively track the tumor cells.
Photo of Glioblastoma Cells From Patient in Brain of a Rodent
The green indicates glioblastoma cells (cells of a malignant tumor that impacts the brain and spine) from a patient that have been placed inside the brain of a rodent, while the red indicates stromal astrocytes (a type of cell within the central nervous system) of the rodent’s brain. (From the Holland Lab website).
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