CAR T-Cell Therapy

Potential cancer therapy? You’ve got yourself a headline. And CAR T-cell therapy, a new cancer treatment, is no exception.

Let’s run through some basics first.

The human body protects itself from harm using its immune system – a group of specialized cells that cooperate to hunt out and destroy potential threats. We tend to think of dangers to our body as something that invades it (like bacteria), but our own cells can become harmful, too.

Cancer. The word alone is enough to make your heart sink.

Scariness aside, cancer is very broad term. It refers to a group of diseases in which your own cells grow uncontrollably. They often form tumours, and can spread to other places in the body.

tumour formation
Image source: Cancer Research UK via Wikimedia Commons

That’s a basic definition, but check out the NCI website if you want to learn more.

Surprisingly, we only recently worked out that our immune system can detect and destroy cancer cells. This led to the development of immunotherapy, a new group of cancer treatments designed to boost our immune system to fight cancer.

Chimeric Antigen Receptor (CAR) T-cell therapy is a type of immunotherapy that has made headlines across the globe. But what is it?

T-cells are part of the immune system, and can recognize dangerous cells in our body. They can destroy them directly, or recruit other immune cells to help finish the job. CAR T-cell therapy involves editing a patient’s T-cells to help them fight cancer.

Sounds complicated. How?

Cells have molecules on their surface that act as markers, telling the immune system what’s going on inside it. Cancer cells often have different sets of markers to normal cells, which can help them to escape the immune system. Now, scientists are trying to use this difference to treat cancer. Here’s how:

First, T-cells are extracted from the patient’s blood. A virus is used to deliver a set of instructions to these T-cells, which tell them how to make a special receptor. Once made, this chimeric antigen receptor (CAR) is put on the surface of the T-cells. The receptor will bind to a certain type of marker on the surface of cancer cells, so the T-cell can recognize them.

Wait…chimeric?

If you’re a bit of a mythology geek, you’ll know that the chimera is a mythical creature made up of bits of different animals. CARs are also a mosaic of different parts, which tell the T-cell to do different things. Together, they increase its ability to destroy cancer cells.

CAR T cell labelled
The different coloured blocks represent the different parts of the receptor. Image by Vanessa Place.

So, we’ve modified the T-cells in the lab so they now have CARs on their surface. These cells are encouraged to grow and divide, then put back into the patient. Hopefully, they will survive in the body. Using the CAR, the modified T-cells should be able to recognize and kill cancer cells. This video sums it all up:

Pretty amazing, right?

The success of CAR T-cells in clinical trials generated a lot of excitement. They are currently only effective against blood cancers, but in the future they may be suitable to treat other types of cancer.

As you’ve probably guessed, CAR T-cell therapy isn’t without problems:

Cost: it’s expensive.

Risk: several people have died in clinical trials . Doctors think this was because the T-cells reacted badly with other drugs given to the patients. Another major risk is a potential side effect called the cytokine storm – an out-of-control response by the immune system that can be fatal.

Should we believe the hype?

As I’ve mentioned in other posts, I don’t believe that all journalists over-hype science news. Yet some do, throwing around words like “cure” that raise hopes prematurely.

Like anything else, CAR T-cell therapy has its drawbacks. Yet, I’m going to stick my neck out and say that I (cautiously) believe in this therapy.

Don’t get me wrong, CAR T-cell therapy is far from perfect. Researchers across the world are still working hard to refine and improve it. It could be a big step on the rocky road to treating cancer.

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The Human Genome Project

For let us be in no doubt about what we are witnessing today – a revolution in medical science whose implications far surpass even the discovery of antibiotics, the first great technological triumph of the 21st century…” Tony Blair

It’s the year 2000. The Human Genome Project announces that a rough draft of the human genome is complete. Sounds important, but what does it mean?

First, back to basics. Remember this?

DNA edited 2
Image source: Seaweed & Co, modified with permission

DNA. That iconic double helix, made of two DNA strands twisted together. Each strand is a string of bases that come together to form base pairs.

There are four different bases, given the letters A, T, G and C. The bases on a DNA strand are arranged into a sequence. In our cells, DNA itself is arranged in more organised structures called chromosomes.

Gene – a region of DNA that carries the information for a characteristic (eye colour, for example) that can be passed on to your children. It’s more complex than that, but we won’t go into the details.

The base sequence of genes can differ, leading to variation. These changes (known as mutations) can sometimes be damaging, and are associated with disease.

The genome of a living thing is its complete set of DNA, containing all the information needed to build it.

So, that’s the end of our genetics lesson.

aint nobody got time for that edited
Image source: Noise Blankers Radio Group via Flickr, modified with permission

If you have got time fo’ that, check out Learn Genetics.

In 1990, scientists across the world began the Human Genome Project (HGP). It had lots of goals, but the main one was to sequence the human genome –all 3 billion base pairs.

FYI: sequencing a genome means working out the order of the bases. Machines can now read the base sequence, like you reading this sentence.

…How?

In the HGP, the publicly-funded groups used hierarchical shotgun sequencing to sequence the genome.

Scientists tackle the genome in sections. A section of DNA is put into a carrier molecule called a bacterial artificial chromosome (BAC). The BAC delivers this section of our DNA to a bacterial cell, which will copy it. These DNA copies are collected, and chopped up into smaller pieces.

We put these fragments of DNA into other (smaller) carriers, that deliver the DNA to bacteria so that it can be copied and collected, like before. Finally, the base sequence is read.

Now it gets tricky. We have all these sequences, but we need to figure out what order they were in, on the chromosome they came from – we need a map.

Not your typical map, but one made up of DNA markers – short DNA sequences with a known location in the genome. Scientists can look for these markers in our DNA sequences, and use them to arrange the sequences in the correct order. Phew.

This video walks you through it:

In 2003 the HGP was declared complete, and the world went nuts. Tony Blair and Bill Clinton had been ready to party since 2000! The sequence of our genome was made freely available on the internet, so anyone could use it, and the possibilities seemed endless.

the HGP books
A print out of the human genome at the Wellcome Collection, London. Image source: Russ London via Wikipedia.

Many people thought the sequence would revolutionize medicine; allowing us to design better drugs, identify mutations linked to cancer, and more. The media was particularly interested in the potential to treat disease. If we understand which genes are associated with a disease, can we cure it?

15 years on, the picture isn’t so clear.

Research has benefited from the HGP – scientists have vast amounts of information about our genome at their fingertips, making it quicker and cheaper to explore it.

To treat disease, progress is slower. There has been progress; understanding the role of a gene in disease helps us to better understand the risk of developing that condition (which can now be explored with genetic tests). But understanding risk isn’t a cure.

Once the excitement about the HGP died down, it became clear that the next task –going from sequence to treatments – was much bigger. This takes time, and has led to some dissatisfied grumblings.

But many (although not all) scientists and journalists made it clear that the sequence was just the beginning. Figuring out what to do with it is another story entirely.

Should we believe the hype?

I find this one difficult to call. The HGP was undoubtedly a huge achievement, but talk of miracle cures and medical revolutions  were possibly too much too soon. Only time will tell…

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