Covid style mRNA cancer vaccines enter clinical trials

We’re going to examine messenger RNA - or mRNA - cancer vaccines. These can help the immune system detect and destroy cancer cells. They work by introducing short pieces of the genetic material mRNA into the body; this is picked up by immune cells, then translated to produce antigens similar to those displayed on cancers. This triggers an immune response against that target, and it’s also how the Covid-19 mRNA vaccines work. Debashis Sarker at King’s College London has been conducting clinical trials for patients with lung cancer, melanoma and other solid tumours and has been telling me how they work…

Debashis - mRNA, it's like an instruction manual or recipe. It tells your cells how to make a specific protein. For a cancer vaccine, the mRNA is the recipe for making a tiny part of that cancer cell, what we call the cancer antigen. When a doctor gives a cancer mRNA vaccine, it basically delivers that mRNA or that recipe into some of your cells, and those cells can read the recipe and make that specific cancer antigen. Once that is made, that is shown to your immune system, just like a wanted poster of the cancer cell. Now that your immune system has seen the abnormal antigen, it learns how to recognise it and your immune system can then go around your body looking for cells that have that same antigen, which are actually cancer cells, and use the immune system to better recognise those cancer cells to try and attack and destroy them.

Chris - How do you pick your target? When you've got a cancer in front of you in a patient, how do you say, well, that's the bit of the cancer I'm going to persuade the immune system to go after?

Debashis - The first is what we call a personalised vaccine where one of the things that we can do is what's called gene sequencing to try and understand what are the abnormal mutations that a cancer cell is producing, and then produce a specific personalised vaccine individual to that patient. That's one approach and certainly there are a number of these mRNA cancer vaccines which have that particular approach. There are other cancer vaccines, more what we call off the shelf vaccines, which look at common tumour antigens which occur across a whole range of different cancers, and using that RNA vaccine technology to target those specific antigens.

Chris - And do you crosscheck to make sure that they're unique to the cancer, these antigens, so you don't then provoke the immune system to go running after your own tissue and effectively cause autoimmune disease, which could otherwise happen?

Debashis - I think part of this is for these types of vaccines to train the immune system to recognise these antigens as the bad guy. One of the theoretical advantages of this type of technology is that it should be very specific for the cancer cells and not target your body's normal cells. The safety of these types of vaccines should be very good because, unlike things like chemotherapy, which are also attacking your body's normal cells, those should be relatively spared.

Chris - You've been running some trials against a range of different cancers, melanoma - a kind of skin cancer - lung cancers and things. You've just been presenting the results of those trials. What have you been showing?

Debashis - The trial that I'm currently involved with is a very early stage trial. It's what we call a phase one trial of a new mRNA based cancer vaccine. The principle behind it is to try and help the body's immune system target and attack cancer cells and it actually is designed to target two specific proteins or antigens, as we've been describing, which can sometimes help the tumour to escape the immune system. So in the trial that I've just presented recently, we've tested this vaccine in patients for the first time. Now, because it's a phase one clinical trial, the main aim of this particular trial is really to test how safe and tolerable the drug is and work out what dose of the vaccine we should be giving. In this particular study, what I reported is 19 patients with a whole range of different types of cancers who had often received multiple types of previous treatment including multiple lots of chemotherapies. This particular vaccine is given as an injection into the muscle every three weeks. What we looked at was how safe the vaccine was, how well tolerated it was, and also whether it was able really to generate that immune response that we wanted to see to be able to take the drug into further development. The findings that I presented were really to show that the vaccine was well tolerated with no serious side effects, which is what we would expect from an mRNA Covid type vaccine. We demonstrated that the drug can activate the immune system in many patients in the way that we would want. In some of the patients that we treated, we were able to show that, for a period of time, the cancer didn't continue to grow in the way that it had been prior to the study. Very preliminary results, but exciting. We are now testing this particular drug in more patients and in particular for patients with melanoma and lung cancers, really to try and see genuinely whether it's effective and can be potentially used as a treatment in the future.

Chris - Have you gone in and taken pieces of the tumours out in these patients to see if you are now seeing an intensification of the immune response which, if the vaccine is provoking the immune system to attack better, perhaps you'd expect to see?

Debashis - We have done that on a small number of patients and in fact that work is ongoing at the moment in other patients who are participating in the trial. What we have been able to see so far in some of those patients is that we've been able to elicit that immune response that we wanted to see in terms of activating those specific immune cells. And also, that impact on what we call the microenvironment: the ability to activate important immune cells against the cancer, but also to down regulate, or to reduce the activity of cells that sometimes suppress the immune system. I think those are important findings that show the validity of this approach. But hopefully with more information coming through from other patients treated on the trial, we'll be able to get more stronger and robust data.