Month: November 2018

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When an Effective Cancer Treatment Makes Your Cells Riot: Cytokine Release Syndrome

Researchers and doctors have found many effective ways to modify cancer patients’ own immune cells and use them to attack cancer cells. They have been so successful that one type of these so-called “immunotherapies” was even considered the “Advance of the Year” in 2018 by the American Society of Clinical Oncology. However, these therapies are not perfect. Some immunotherapies cause overactivation of the immune system, which can result in terrible side effects including damage to internal organs. Cumulatively, this overactivation and its side effects are known as cytokine release syndrome. Thankfully researchers are coming up with inventive ways to limit or stop cytokine release syndrome, which makes immunotherapies even more powerful.

Researchers don’t yet fully understand all the specific activities that cause the dangerous overactivation of the immune system during immunotherapy. You can think of this overactivation as something like a riot or stampede of cells. When doctors give cancer patients modified immune cells, they do a fantastic job of killing cancer cells, but they also sound the alarm and throw out a bunch of signals saying “SOMETHING NEEDS TO BE DONE!” These signals activate other immune cells, those immune cells send out more signals, and then even non-immune cells can begin acting irregularly.

Drawing a modified immune cell attacking a cancer cell and causing a riot
A cellular riot caused by a modified immune cell used to attack a cancer cell

This cellular rioting can lead to disruption of blood vessels, flu-like symptoms, and damage to organs; but, luckily, doctors know how to treat many of these things. Doctors can give patients drugs that will limit the negative side effects of the cellular riot and block some of the alarms. Nonetheless, these drugs aren’t equally effective in all patients, and there is no one-size-fits-all treatment that can be used in every case.

Recognizing this issue, researchers are working to make it so the modified cells used in immunotherapy don’t cause cellular riots. These researchers are further modifying the immune cells so that they send out fewer alarm signals in the first place and can be destroyed if a riot begins.

Importantly, even without these new modifications, immunotherapies are already very effective at treating cancers of the blood (read the Advance of the Year article for more). I’m hopeful that researchers will be able to make immunotherapies more effective against other types of cancers soon (think solid tumors), and the ability to control these cellular riots will be the icing on the immunotherapy cake. It’s an exciting and hopeful time for cancer researchers and patients!

References:

  1. Chakravarti, Deboki, and Wilson W. Wong. “Synthetic biology in cell-based cancer immunotherapy.” Trends in biotechnology33.8 (2015): 449-461. PubMed PMID: 26088008. PubMed Central PMCID: PMC4509852.
  2. Shimabukuro-Vornhagen, Alexander, et al. “Cytokine release syndrome.” Journal for immunotherapy of cancer 6.1 (2018): 56. PubMed PMID: 29907163. PubMed Central PMCID: PMC6003181.
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Bacterial Abilities in the Gut: Stealing Vitamin B12

Bacteria are cool. They can do all sorts of things that you might not normally think about as you kill millions of them with your favorite antibacterial soap. Some bacteria can break down and eat toxic wastes. Some bacteria can use sunlight and carbon dioxide to grow. Some bacteria can even be used to create medicinal compounds. Although we know a lot about what bacteria can do, we still need to learn a lot more in order to effectively solve the world’s problems. Bacteria are everywhere and will therefore somehow be involved or interact with any technique used to solve problems like global warming or disease.

Importantly for this post, it’s estimated that there are TRILLIONS of bacteria throughout the human gut and we are far from understanding all of the beneficial and dangerous things they can do. As a small but meaningful step in the right direction, researchers from Yale University recently discovered that bacteria in the human gut can grab and use vitamin B12 coming from our food. Essentially, these bacterial pirates can steal vitamin B12 that would otherwise be absorbed in the small intestine, but this isn’t necessarily a bad thing.

A bacterial pirate steals vitamin B12 from the human gut
A bacterial pirate steals vitamin B12 from the human gut

To steal vitamin B12, these bacteria create a protein that latches onto the vitamin really tightly thus allowing the bacteria to pull the vitamin into their cells and use it for growth. While they may be pirating some vitamin B12 from us, these bacteria also don’t survive well in the gut if they lose the ability to steal from us. Given that these bacteria likely play important roles in helping us digest foods and maintain healthy mixtures of bacteria in the gut, we can forgive them a little bit of pirating.

Now that researchers know how these bacteria grab onto vitamin B12, they might be able to use this knowledge to prevent the bacteria from stealing B12 in humans who don’t get enough B12. They could also potentially use this information to create new therapeutic bacteria that are better at surviving in the gut. For example, if researchers wanted to engineer bacteria that could live in the gut and create a nutrient for us, they might give the engineered bacteria the ability to steal B12 so that they are better at surviving in the gut. The researchers could also make it so they could shut off the stealing ability. If things started to go wrong, the researchers would just shut off the bacteria’s stealing ability and they’d be eliminated from gut.

As you can see, many new opportunities have been opened up simply from learning a little bit more about what bacteria can do. At first glance, the ability to steal B12 from us seems like it must be a bad thing, but, not only does this ability help useful bacteria survive inside of us, it potentially gives researchers new ways to manipulate bacteria for beneficial purposes.

I’m hoping to write more about cool bacteria and all the things they can do in the future so stay tuned!

References

Wexler, Aaron G., et al. “Human gut Bacteroides capture vitamin B12 via cell surface-exposed lipoproteins.” eLife 7 (2018): e37138. Pubmed PMID: 30226189. PubMed Central PMCID: PMC6143338.