Harnessing the immune system to combat cancer

A way to target cancer by re-programming the immune system to attack tumours has been discovered by scientists in the US...

Using a "supramolecule", researchers at the University of Massachusetts Amherst were able to enhance the anti-tumour activity of immune cells called macrophages. This halted tumour growth and increased survival in mice with certain forms of cancer.

Macrophages form a key part of the body's first line of immune defence against entities that the body recognises as "foreign". This includes viruses and bacteria, but also cancer cells, which macrophages normally destroy by ingesting them. But cancer cells frequently side-step this process.

"Cancer can overcome the attack by macrophages using two main mechanisms," Ashish Kulkarni, who led the study, explains. "One, it can convert macrophages into a version of these cells that do not really target the tumour. The other way is by sending a signal to the macrophages that says ‘don’t eat me’".

So how have the team overcome this? "What we wanted to do was to outsmart the cancer cells by targeting both of these mechanisms at once," says Kulkarni. "We converted benign macrophages into aggressive antitumour macrophages, and we also blocked the ‘don’t eat me’ signal. This made the macrophages ready to attack."

This was achieved by delivering two drugs to the tumour simultaneously in the form of a supramolecule. "We designed a material that works like lego blocks, with different ‘building blocks’ that can serve different purposes. So we used two different drugs that can ‘click together’ and then target the macrophages." Each of the drugs targeted one of the mechanisms respectively.

The approach worked. "In mouse models of breast cancer and melanoma, this targeting of two pathways simultaneously with the supramolecule was shown to inhibit tumour growth. We also inhibited the spread of tumour cells to distant organs, known as metastasis. We have also shown that this method increases survival as compared to current therapies," says Kulkarni, adding that though these are preclinical studies, he expects to see the fist clinical studies of this therapy happening within the next three to five years.

Kulkarni believes many stand to benefit from this treatment once it is fully developed, as it has applications in a wide range of cancers.

"The majority of solid tumours have been shown to have large amounts of macrophages. Breast cancer and melanoma are two examples, but macrophages are also found in pancreatic cancer, bladder cancer, prostate cancer, even cervical cancer. So we are hoping that this therapy can be used in a large variety of solid tumour types."

According to Kulkarni, the future of cancer therapy lies in using immunotherapy and more traditional cancer therapies, such as chemotherapy and radiotherapy, in combinations which are specifically tailored to each patient’s cancer type.

"The right combination of therapies for the right tumour types really is the future," he says. "A one-size-fits-all approach is not going to work in cancer, so having an approach where we know which patient is most likely to respond to which therapy, and what combinations of therapies need to be used, will likely have a major impact in clinics. This is something that we are hoping to work on in the future..."