Decoy bacteria and tiny 'nanobodies' paired up to fight cancer in new technique

A young Indian researcher in the US has turned harmless bacteria into a potential cancer-fighting army, by designing ‘nanobodies’ – molecules smaller in size than the antibodies our body produces to fight off infections and illnesses. These nanobodies can quietly sneak up to cancerous tumour cells and mark them for destruction by agents of the body’s immune system. The clever twist and novelty in this strategy is the use of a harmless bacteria, Escherichia Coli, to do the cancer-fighting. It was tested in mice that had cancer in its disease-fighting ‘lymphatic’ system, known as a lymphoma. Currently, lymphomas are treated with a suitable combination of chemotherapy, medication, radiation and stem-cell transplants in cases. But safer and more efficient methods are now on the horizon to treat cancers. The bacterial decoy/nanobody treatment, for instance, makes use of a pool of carefully-selected monoclonal antibodies (mAbs), all of which are exact copies, or clones, of each another. This army of clones can take down a cell or tissue it is built to target based on protein ‘signatures’ that are unique to cancer cells.

Monoclonal antibodies have been widely used as a therapeutic tool in cancer research because it has successfully suppressed the growth of tumours. A combination of different strategies like specifically targeting cancerous cells, pumping these cells with toxic compounds, changing how the body’s immune system responds, and redirecting the body’s immune cells towards cancer cells. Solid cancers are very dependent on the formation of new blood vessels to nourish a growing tumour. This process of “angiogenesis” is much faster around rapidly-growing cancer cells than other healthy cells in the body, which inspired researchers to develop inhibitors of angiogenesis. Though mAbs are used to fight many different illnesses, they are often complex and too large to become a widely-used therapy. Much like electronics in the digital age, antibodies to treat cancer — including those to stop blood vessel formation – are also awaiting an upgrade. In the case of medicine, faster, safer and smaller are all steps in the right direction for treatments. Miniaturised antibodies are already a reality. Nanobodies (Nbs) are tiny fragments of the original antibody that has been reduced to only its essential components. Now, Nbs are promising in both therapy and diagnostics in cancer because of their tiny structure and unique function. [caption id=“attachment_6112021” align=“alignnone” width=“1280”] An immune cell known as the T-cell (green) shown attacking a cancer cell in an illustration. Image credit: Lab Roots[/caption] “Many tumour cells have this CD47 molecular tag on them. Through this tag, the tumours send a ‘don’t eat me’ signal to the immune system,” Sreyan Chowdhury, a doctoral researcher at Columbia University, New York, told The Telegraph. “The nanobody we send as cargo through the bacteria blocks the tag and renders the tumour cells vulnerable to attack by the immune system.” The bacteria were genetically modified to carry a ’nanobody’ to the tumour they colonise. As they grow, a certain threshold population of bacteria is reached, after which these cells break open and release the nanobody into its immediate environment: the tumour. This method of drug delivery can be used by any antibody-centric therapy for cancer, which makes it an exciting new application of bacteria and medicine. Independent medical researchers at Harvard, Michael Dougan and Stephanie Dougan, commenting on the reprogrammed bacteria-delivered antibodies, said they represent a “major engineering accomplishment”,  the Telegraph said. One of the biggest advantages an “immunotherapy” that uses antibodies is that its action is very, very specific, at the site of the tumour. This lowers any side-effects from treatments like chemotherapy, which affects healthy organs, too.