Cancer and Mutations
At its core, each cancer cell is just a malfunctioning cell. Cancer cells grow and reproduce tirelessly, while draining resources without producing anything for the body, to an extent that is dangerous. This abnormal growth and reproduction is caused by one thing: mutations.
Mutations happen multiple times in every day, however, the only mutations cause a cell to become cancerous are in proto-oncogenes. Proto-oncogenes are genes that, when mutated, have the ability to cause unnecessary and dangerous growth or reproduction in a cell or allow it to reproduce with mutations. Take, for example, the p53 gene. p53 is crucial to the reproduction of the cell; if a cell has any significant abnormalities or mutations (especially those in other reproductive genes), the p53 protein (which is produced by the gene), can arrest cellular reproduction and force the cell to kill itself in order to prevent the cancerous mutation from spreading. The reason many of the mutations that occur every day don’t cause cancer all the time is because many tumor suppressor proteins like p53 stop the mutations from spreading before they become a dangerous problem. However, if there was a mutation in p53, the cell would be able to reproduce unchecked, effectively making it cancerous.
How The Vaccine Works
Mutations in cancer cells can have both benefits and disadvantages for the immune system. Often, these mutations produce neoantigens, proteins that allow the immune system to identify that a cell is cancerous. However, sometimes, the cancer cell is able to evade the immune system using these mutations. To understand why cancer cells are able to do this, we have to take a look at T-cells.
T-cells are the guardians of our body, protecting us day and night. They go to each cell, latch on, and check for any signs of cancer or pathogens; if any are found, the cell is immediately destroyed. Normally, this works, and the cancer is successfully vanquished. However, sometimes, cancer cells can evade this. Cancer cells can overexpress a protein called PD-L1 (Programmed death-ligand 1). When the T-cell comes to inspect the cancer cell, a T-cell receptor called PD-1 (Programmed cell death protein 1) recognizes the PD-L1 and mistakenly thinks that it is a healthy cell. This allows the cancer cells to continue to grow and reproduce untouched.
However, the researchers came up with an ingenious way to circumvent this. In order to create the vaccine, they analyzed the genome of cancer cells in each patient using a machine learning algorithm in order to find 15–20 of the neoantigens that would be most likely to bind with the T-cells in the body. These neoantigens were modified and then deployed near the cancer cells so they could block the receptor site of the PD-L1. That’s why this vaccine is a double edged sword: not only does it prevent the cancer cells from identifying themselves as normal, but it also heightens the likelihood that the cancer cells will be detected and eliminated by T-cells.
The best part is that the effect of the vaccine sticks. Once a neoantigen is recognized by a T-cell, it will then go on to activate a memory B-cells after killing off the cell presenting the antigen. The immune system safely stores memory B-cells, which, if the neoantigen is ever recognized again, will immediately proliferate into many plasma cells. Plasma cells rapidly release antibodies, which seek out the offending antigen and attach to it, making it easier to identify and neutralize the antigen presenting cell.
After being treated with the vaccine, patients’ immune system cells were active not just against tumor cells flagged with the specific neoantigens in the vaccine but also other proteins that could identify the tumor cells. All of the patients, who originally had stage III or IV melanomas, were alive four years after administration of the vaccine. Six even had no sign of the cancer. This is amazing, considering stage IV melanomas have around a 15% five year survival rate.
This vaccine, called NeoVax, has the potential to be a game changer in the field of cancer treatments if it can be applied to other cancers, especially far deadlier cancers than melanomas.
References
https://www.nature.com/articles/s41591-020-01206-4
https://blog.dana-farber.org/insight/2019/09/making-the-immune-system-work-against-cancer-cathy-wu/
https://www.sciencedaily.com/releases/2021/01/210121131857.htm
