Cancer vaccine?? What the what??

Cancer vaccine?? What the what??

When the phrase “cancer vaccine” appeared in my inbox (YES I get nerdy emails about the latest nerd stuff), I scoffed. Yeah RIGHT let’s take a look, I told myself. People…as I live and breathe…this is really happening.

I was skeptical because vaccination is so specific. Inactivated or impaired microorganisms are injected into your body to prepare the immune system. If the exact same bacteria or virus actually infects you, your immune system says “WOA WOA WOA, I’ve seen you before, ya tiny bastard” and destroys it. Would a cancer vaccine be restricted to similar specificity? Only the breast cancer vaccine could prevent breast cancer?

The answer is shockingly NO. In mice, injection with the cancer vaccine prophylactically prevented tumorigenesis of breast, skin and lung cancers. How could this be possible?? What the heck is this magical vaccine??

About 12 years ago, scientists discovered that they could reprogram human cells into their stem cell progenitors and coined the term “induced pluripotent stem cells” or simply iPSCs. Forcing the expression of a specific cocktail of proteins in skin, blood or kidney cells was able to straight up Benjamin Button them back into their blobby “embryonic” state. Not only do iPSCs completely forgo any ethical murkiness of using actual embryonic stem cells, they have great potential on the horizon of personalized medicine. With the ability to isolate specific diseased cell types and reprogram them, scientists dreamed of treating a myriad of ailments from diabetes to Alzheimer’s.

With the discovery of iPSCs, some smart and historically-minded scientists remembered something very important. Over ONE HUNDRED YEARS AGO scientists found that injecting mice with embryonic tissue prevented the growth of transplanted tumors. Putting two and two together….maybe induced stem cells INSTEAD of embryonic stem cells would work! And they DID. After irradiating the iPSCs (to degrade their DNA and prevent the iPSCs themselves from causing cancer), they can be injected with a splash of CpG (a classic immunostimulatory molecule to say “hey immune system, come look over here”) into mice to substantially prevent tumor progression.

Adapted from Kooreman et al 2018.

The reason iPSCs are an effective vaccine is because they prepare the immune system to quickly eradicate growing tumors. The reason they can prepare the immune system…is because stem cells look more like cancer cells than normal tissue! Stem and cancer cells have overlapping gene expression, suggesting cancer itself is a reprogramming event that allows for de-differentiation, just like the induced stem cells. Intricate, established tumors actively depress the local immune system, which can explain why iPSC injection was not effective at clearing previously entrenched tumors. BUT another amazing use for an iPSC vaccine is to prevent reoccurrence. Once the primary tumor is surgically removed, injection with iPSC prevents regrowth of the cancer. If this replicates in humans, it could revolutionize how we treat cancer.

This is actually a huge obstacle: will this effect replicate in humans? The concern about jumping from mice to humans is something called a “cytokine storm”. Overstimulating the immune system could induce a systemic release of cytokines that leads to organ toxicity, which actually has occurred in other cancer vaccine attempts.

My final question is why T cells recognize the induced stem cells in the first place. If there is cross reaction between the iPSC vaccine and normal human stem cells, which are usually found sneaking around in the bone marrow, it could potentially be dangerous and lead to an autoimmune disease. As T cells grow up from baby T cells into #adulting T cells, they pass through the thymus to make sure they dont target normal body cells. It must be why the CpG adjuvant is necessary to enhance the reaction. AND why scientific/clinical trials are so important!! Hopefully further research will verify the safety and efficacy of iPSC vaccination in humans. If so, I think we have a solid shot at knocking cancer down a few notches. Let’s hear it for a century of knowledge paying off! Yay science!

Cheers to JB this week for being a great pal. And for buying me a boozy lunch last friday! Bad news tastes better with beer. Amiright?

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