Cancer and the immune system – illustrated! (Part 2: Vaccine therapies)

In Part 1 of Cancer and the Immune System – Illustrated, we had a look at how the immune system naturally responds to cancer, and how crafty cancer cells evolve to hide from the immune system. We also went into how researchers have harnessed the power of synthetic antibodies in the fight against cancer.

We’ll continue learning more about how researchers are unlocking the power of the immune system to fight cancer, this time focusing on vaccine therapy and cell transfer mechanisms.

When you hear the term “vaccine,” you probably think about your annual flu shot, or kids getting vaccines to pre-educate their immune cells and prevent later infection. These are “preventative vaccines.” In this post we’re going to talk about “treatment vaccines,” which are designed to treat already-established disease.

A vaccine is a substance that, when injected into a body, stimulates immune cells to be on high alert for a target so that the immune cells activate more quickly and powerfully when they see it. A vaccine generally included pieces of the target plus an immune cell stimulating factor (“adjuvant”-we’ll talk about what this is and how it works, too). Let’s explore this more!

Recall our villain from the previous post, cancer cell:

cancer_cell

There are a couple of ways scientists can make the cancer vaccines that will stimulate the patient’s immune cells. They can take samples of the cancer cells, kill them; they can create short pieces of protein that are part of the cancer cell’s mutated protein code; they can use DNA or RNA (raw genetic code) that corresponds to the mutated cancer protein. In all of these cases, harmless parts of the cancer cell are mixed with an extra stimulating factor (“adjuvant”) and injected into the patient. (Click to enlarge any of the images in this post.)

cancer_vaccine

What happens once it’s injected? Your “big eater” immune cells (“phagocytes,” such as macrophage and dendritic cells) gobble up the pieces of cancer cell that were in the vaccine, since they’re always gobbling and sampling from their environment. They digest it into smaller pieces, and show off the smaller pieces of cancer proteins so that T cells can come have a look. Remember from the first post that phagocytes show off these pieces of bad guys with arms we call “MHC receptors” that only T cells can scan.

phagocyte_eats_vaccine

And wait, whoa, what’s going on in it’s tummy there? (Technically, the “endosomes.”) Let’s zoom in:

endosomes

Remember those immune cell stimulating factors, the adjuvant? They bind to receptors in the endosomes and send “go, go, go!” signals. One of the adjuvants that’s showing great promise in trials is called “CpG.” CpG is a stretch of DNA that is rich in C and G’s in its sequence, and these CpG-rich stretches are commonly found in viruses and bacteria. It’s a conserved pattern that has been found in viruses and bacteria for ages, and our immune cells have evolved to recognize these right away as a sign of an invader that needs to be destroyed. So scientists are leveraging this natural pattern as an “adjuvant” – as a way to boost the immune response to the cancer proteins.

Ok, so the phagocytes are now showing off the chewed up pieces of cancer cells. Enter: T cell:

phagocyte_cancer_t_cell

T cell detects something “not normal” and signals for other immune cells to activate, and this starts an inflammatory cascade where your immune system begins fighting the cancer cells that also have the mutated protein that is being shown off.

If you were reading closely in the last post, you’re probably wondering why T cell isn’t shooting toxic pellets at the phagocyte. The type of T cell that is activated depends on the route of entry of the bad guy, and in this case, a phagocyte eating the cancer proteins in the vaccine results it in being shown off in a “MHC receptor” hand that only “Helper T cells” recognize, not the toxic pellet-shooting “Cytotoxic T cells.”

In addition to all of the above, there is another similar approach where, instead of injecting cancer protein and adjuvant, you inject (at the site of a tumor) adjuvant and a chemical that kills cancer cells, thereby exposing the cancer proteins for the phagocytes to eat up.

And there you have how cancer treatment vaccines work! Inject pieces of the cancer cell so your immune system can be trained on what it looks like, and combine that with an immune cell stimulating “adjuvant” to make it go, go, go.

Learn more in summary form, or in via a technical review!

If you’ve enjoyed and learned from this post, please consider supporting my Kickstarter campaign to help fund publishing and distribution of my illustrated immunology book! :)

Immunology_Educaition

Continue on to Part 3.

Angela

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4 thoughts on “Cancer and the immune system – illustrated! (Part 2: Vaccine therapies)

  1. Robert Gillis says:

    “adjuvent” should be adjuvant throughout.
    (5 instances )

    Only mentioned because i really enjoyed your 3 part article!

    I hope you post more. I am interested in the MOA for intralesional rose bengal as monotherapy and with anti-PD-1. Moffitt has just presented a poster at AACR that is very exciting. It appears that the injected rose bengal soution results in a high ratio of infiltrating CD8+ T cells to Treg cells. The RB solution lyses the cells and allows the neoantigens of all the heterogeneic cells that it penetrates. This study reveals that RB is an unprecedentedly efficient presenter of malignant antigens to the immune system. Pretty heady stuff!

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