Professor Catharina Svanborg, a professor of immunology at Lund University in Sweden, speaks to BBC Science Focus commissioning editor Jason Goodyer about a molecule from breast milk with remarkable tumour killing properties dubbed ‘HAMLET’ – short for human alpha-lactalbumin – undergoing its first human trials.
How did you find HAMLET?
We were looking for natural antibacterial molecules in body fluids. We threw some lung cancer cells into the test tube with human milk and noticed that the tumour cells died. We had to repeat it a few times before we could believe our eyes.
Was it just raw human milk?
No, it wasn’t actually. Human milk is a source for all sorts of molecules – obviously, it’s a wonderful mix of molecular protection for babies. But we were using different fractions of it, because either you have antibodies, or you have small molecules, or you have sugars, or lipids. Depending on which fraction you’re using, you can get very different results. It turned out that one of these fractions was causing the tumours to die, but not whole milk as it comes out of the breast. It has to be treated a little to bring out the HAMLET molecule.
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How exactly does it work?
HAMLET has multiple effects on tumour cells. Cancer cells have a more primitive membrane than normal differentiated cells and it appears that HAMLET benefits from this. It inserts itself into the membrane and starts ion fluxes across it. Then, in the nucleus it binds to the very substance that the DNA and the proteins in the nucleus make. So, it’s a bit like pouring cement on these cells. They just can’t make new molecules and survive any longer.
So what is this compound’s purpose in the breast milk?
We’ve been trying to focus on the local effects in a baby’s large intestine. There can be virus-infected cells in the intestine that need to be removed, instead of developing to become more mature, they could start to look like cancer cells. So, you could think of these HAMLET molecules as scavengers that remove cells like this that go the wrong way. There is also previous data on breastfeeding being protective for childhood lymphomas and certain kinds of intestinal cancers.
I gather you’ve already run a number of in-vitro and animal trials?
Yes. The in-vitro trials were exhilarating because we used a range of different cancer cell lines. Most of them are what we call carcinoma, so they are from tissues that develop into cancers. But we also looked at leukaemia and others. And to our great surprise most of these different cancer cells died in a similar way. We call it ‘apoptosis’ and it makes us think that we might be developing a molecule that presses some button in tumour cells. And so, the experiments in test tubes are very promising.
Of course, one cannot set up 40 different cancer models, but we have looked at quite a few. One is brain tumours where the model is that you remove the human tumour during surgery and you put it into an animal for it to develop. Then you treat the animal by local injection of a drug into its brain. This is the model that has been developed quite recently and it’s very promising.
The second one that we did was colon cancer and the third one was bladder cancer in mice, where large tumours can develop quite rapidly. And if we inject HAMLET, or our now second-generation synthetic drug, into these mice, we can see a very potent, dose-dependent therapeutic effect.
Can you use a synthetic version of breast milk?
Yes, we were fortunate in that the part of the HAMLET molecule that can be synthesised is the part responsible for the activity. This now being produced in state-of-the-art factories with sterility and all the other things that we need.
Have you carried out any human trials?
We’re due to finish our first at the end of June and are looking forward to getting the data. It’s a double-blind placebo control trial, so we have no idea who is getting the drug and who isn’t. The patients have what’s called superficial bladder cancer, and, in part, we selected this variety because we have previously performed an academic human study in bladder cancer and have seen some positive effects, so it was considered that the most realistic indication for this type of trial.
We’re already very happy, because there is no evidence of severe side effects, which is quite a relief. And then, of course, we’ll have to wait and see if the patients really benefit from this treatment.