Peptide vaccines can boost immunity against certain cancers
Cancer peptide vaccine cancer vaccine

Peptide vaccines can boost immunity against certain cancers

Dr. Talia Henkle
Dr. Talia Henkle

In 10 seconds? Deeper knowledge of how genetic differences between people affect the immune system’s response to cancer is leading to the design of new anti-cancer vaccines.

What’s the story? In our Immunity vs Cancer series, we talked about the important role that immune cells called T cells play in protecting us from and even killing cancer cells. On that note, a lot of research is being done to develop vaccines that can direct our T cells to kill existing cancers (called therapeutic cancer vaccines). In this recent study, scientists who had been studying the details of how T cells might work to recognize and kill a certain type of blood cancer  have made progress towards developing a vaccine to help treat these cancers.

What sorts of details did they study? Alas, to understand this we must now dive into the exciting world of MHC (major histocompatibility complex) biology. As a reminder from our T cell digest, to ensure our cells are following the rules dictated by our DNA, every cell in our body (with some rare exceptions) must report its ongoings by coating itself with a visible ledger of its operations (yeah, it’s may look a bit authoritarian but it also looks like accountability). What it means is that almost every product manufactured by the cell (AKA every protein) must be reported to our immune system.

So, why is this “reporting” relevant or connected to getting cancer? This process uses internal reporting hardware, called MHC, that displays small pieces of every protein made (AKA peptides) on the cell surface. Like suspicious government agents, T cells circulate the body and scan the surfaces of each cell to make sure the peptides displayed on MHC are accounted for in the DNA handbook. If not, as would be the case for mutated or viral peptides, the T cells will launch an attack to take out that rogue cell and others like it.

MHC molecules (green) display peptides (red) to T cells. If the peptides are from pathogens or mutated proteins they can activate T cells to kill cells harboring these mutant proteins.  Source: Kaiser, 2022

OK, so malicious cells get dealt with and that’s it? Now, throughout the human population, there are many different types (classes) of MHC molecules, and each class prefers to display its own flavor of peptide. As luck (or, more accurately, biophysics) would have it, some types of peptides are great at kickstarting immune responses while others are not.

Are you getting to the point, finally? Almost there. Researchers identified a certain mutated protein that is known to play a role in causing some blood cancers. Next, they went as far as to discover exactly what peptides (AKA what sections of this protein) displayed on MHC were associated with an anti-cancer immune response (AKA what peptides would activate T cells to kill these cancers). What's more, is that they found that people who develop these blood cancers are more likely to have MHC molecules that cannot display these specific peptides.

So, how can all this cell biology then help patients? Well, the researchers hypothesized that if they engineered their own anti-cancer peptide so that it could bind to other types of MHC molecules, then that peptide could be administered as a vaccine to treat this type of blood cancer (essentially hacking the MHC system to work in favor of patients since people with these cancers don’t naturally develop these anti-cancer peptides). They tested this hypothesis out in mice and saw that combination treatment of an engineered peptide vaccine with immune checkpoint blockade could cure similar cancers in mice.

Good! Can you recap why this is new and exciting? This study is a testament to advances in our understanding of cancer immunology. Not only can we now use genetics to determine if our MHC molecules put us at risk for certain cancers, but we have also advanced our technology so far that we can better predict what types of peptides will bind to different classes of MHC, build those peptides, and use them to treat cancer. While this method still has plenty of room for improvement (only one of ten mice was cured) before it makes its way to patients, it's an important step forward for personalized cancer treatment.

The reason for MHC biodiversity

In the human population, there are more than 200 types of MHC molecules (each person has 6).

The diversity of MHC molecules and hence the diversity of peptides they can display is an evolutionary protective mechanism for humans as a species because, as this paper highlights, not all peptides from dangerous proteins are good at kickstarting immune responses.

As the COVID-19 pandemic taught us, there are always new foes cropping up. With so many different MHC molecules that each select unique peptides to present to our T cells, there is a high probability that at least some of them will be able to successfully activate T cells against whatever nature throws at us.

Dr. Talia Henkle has distilled 4 research papers saving you 14 hours of reading time.

The Science Integrity Check of this 3-min Science Digest was performed by Flávia Oliveira Geraldes.

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