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Immuno-oncology: All you wanted to know but were too afraid to ask

Essentially, immuno-oncology involves developing drugs that use the body’s own immune system to fight cancers

cancer cell
Using the body’s own defences has inherent benefits over traditional treatments

The world’s biggest pharma companies are pouring hundreds of millions of dollars into developing new immuno-oncology drugs – but what exactly are they?

Immuno-oncology is an exciting – and relatively new – type of immunotherapy that is specifically designed to fight cancer.

Multi-billion-dollar business 

Unlike traditional cancer treatments such as chemotherapy, which essentially poison the body in a bid to kill off the tumour, immunotherapies work by stimulating the body’s own natural responses.

For a host of reasons, cancerous cells can sometimes go undetected by our immune systems, but immuno-oncology drugs help to lift this ‘cloak of invisibility’ and encourage the body to attack the cells.

This has obvious advantages given there is no need for invasive surgery or courses of toxic chemotherapy or radiation.

The first immuno-oncology drug was approved back in 2010 - sipuleucel-T for prostate cancer - and since then dozens have come to market, proving effective in treating melanoma (skin) and lymphoma (blood), as well as lung, breast and several other types of cancer.

There is more than just one type of immunotherapy as well.

CAR-T therapies

CAR-T therapies made headlines here in the UK towards the end of 2018 when UK regulators reached a deal over pricing with pharma giant Novartis for its cutting-edge Kymriah treatment.

Kymriah is what’s called a CART-T therapy, which stands for chimeric antigen receptor T-cell.

As the name suggests the technology involves T-cells, white blood cells that help the immune system fight disease and infection.

CAR-T therapies re-engineer the blood to recognise cancer cells that have been hiding in the body that haven’t been destroyed.

This area of immuno-oncology has become a popular field of research with UK companies at the forefront of some of the latest innovations.

Several UK firms in CAR-T space

Leading the pack is Autolus Therapeutics, a spin-out from University College London, which is now listed in the US with a market capitalisation in excess of US$1bn.

Backed in its formative stages by Arix Bioscience PLC (LON:ARIX) and Neil Woodford’s Patient Capital, it is running five CAR-T programmes covering six blood-borne cancers and solid tumour indications.

Smaller, with a market cap of US$110mln, but a potential pocket rocket is AIM-listed MaxCyte Inc (LON:MXCT).

It recently started dosing the second cohort of patients in the phase I clinical trial of MCY-M11, a chimeric antigen receptor that targets solid tumours.

Monoclonal antibodies

There are also monoclonal antibodies, which help the immune system to spot and kill cancer cells. If a company’s drug ends in -mab (tremelimumab, for example), it’s probably a monoclonal antibody.

One of the best things about our immune system is its ability to tell the difference between normal and harmful cells. It uses checkpoints to do just that, which either turn up or turn down a signal.

But cancer cells are clever things, and they can often interfere with the responses to avoid detection.

Monoclonal antibodies trigger the immune system by attaching themselves to proteins on cancer cells, making it easier for the body to find and attack the cancer cells.

Checkpoint inhibitors are the big money-makers

Checkpoint inhibitors are a particular type of monoclonal antibodies that help to flag up cancer cells to the immune system.

Cancer Research has a particularly good analogy: cancer can sometimes push a stop button on the immune cells, so the immune system won’t attack them. Checkpoint inhibitors block cancers from pushing this stop button.

Merck’s Keytruda is probably the most well-known monoclonal antibody. It is what’s known as a PD-1 inhibitor, and sales of the drug doubled last year to over US$7bn.

Peak sales could be as high as US$16bn, according to some analysts, as it takes a stranglehold on the massive lung cancer market.

Bristol-Myers Squibb’s rival PD-1 inhibitor, called Opdivo, used to be the biggest, but it was overtaken by Keytruda last summer. Still, at just shy of US$7bn, it wasn’t too far behind.

Cytokines

Cytokines are a bit more complex to explain. In simple terms, they are a group of proteins that play an important part in boosting the immune system.

They have a lot of control over the body’s response to an antigen – a toxin or foreign substance which causes the immune system to start making antibodies.

If there is an imbalance or their production is altered, this can lead to tumours developing.

Scientists have developed man-made versions of interferon and interleukin, which are types of cytokines found in the body.

On the flip side, if the body is producing too many cytokines, Janus Kinase (JAK) inhibitors can stop the proteins from being excessively activated. These have proved useful in treating cancers like renal cell carcinoma and melanoma.

Sareum Holdings PLC (LON:SAR) is among those developing TYK2/JAK1 inhibitors. In fact, it has two of them, SDC-1801 and SDC-1802.

Preclinical programmes have been mapped out for each discovery with the aim of getting them into the clinic in 2020.

Vaccines

There are also some cancer vaccines, although it is important to note that these don’t work like regular vaccines.

Rather than working to prevent an infectious disease, they are used to stimulate an immune response to attack existing cancer cells.

Once injected into the bloodstream, cancer vaccines should activate an immune response to help fight the cancer.

GlaxoSmithKline PLC (LON:GSK) makes one of the most well-known cancer vaccines called Cervarix.

It is designed to prevent infection from certain types of human papillomavirus (HPV), which is responsible for around two-thirds of cervical cancer cases. Last year, it brought in sales of US$175mln for GSK.

It’s not just the big boys…

While the likes of GSK, AstraZeneca PLC (LON:AZN) and Merck might have more high-profile - and expensive - programmes in the works, there are plenty of smaller companies out there looking to rise up the ranks.

TIziana Life Sciences PLC (LON:TILS) is one of those. One of the drugs it is taking through the clinic is Milciclib, a cyclin-dependent kinase (CDK) inhibitor.

It works to reduce levels of microRNAs in the body, which are thought to help supply blood to tumours. Interestingly, it also a potential tyrosine kinase (TYK) inhibitor.

There’s also Scancell Holdings PLC (LON:SCLP), which is working on two immuno-oncology technologies called ImmunoBody and Moditope.

The drug furthest down the clinical pathway is SCIB1, an antibody that stimulates the immune system to attack tumour cells expressing certain antigens.

A phase II trial of SCIB2 in skin cancer is due to get underway within a matter of weeks.

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