Promising new avenues are being explored in the field of cancer research, thanks to synthetic biology, i.e. the genetic “reprogramming” (in the lab) of living cells like bacteria, transforming them into true and proper anti-cancer drugs. A significant example has been given by bioengineers from Columbia University in New York (USA), who have managed to modify a strain of Escherichia coli bacteria, creating “factories” for the production of antibodies capable of stalling various types of cancer, at least in animals. These antibodies – as reported in the scientific journal Nature Medicine – are highly specific and tiny, so much so that they have been called nanobodies.
How do they work? To understand this (complex) “mechanism”, we need to take into account that cancer cells often “compromise” the reactions of the immune system (our defence system, which ought to eliminate the cells), by exhibiting large quantities of several particular proteins on their outer membrane, including the protein known as CD47. This molecule contains a kind of message that says, “Don’t eat me!” and in fact, when they come across CD47, macrophages (the “fundamental “policemen” of the immune system) are blocked and prevent the destruction of the cancer. The researchers from Columbia University therefore decided to insert a fragment of genetic code inside the Escherichia coli that encouraged the bacteria to produce nanobodies against the CD47 protein.
In addition to this, the bioengineers also added other genetic instructions that caused the bacteria to die (apoptosis), after having generated an adequate quantity of nanobodies. The bacteria modified in this way was then injected into lab animals and quickly reached the tumor without damaging other tissues (in actual fact, the bacteria infected the tumor). At the same time the bacteria produced large quantities of anti-CD47 nanobodies – as the researchers expected. When the bacteria “exploded” due to the effect of apoptosis, the nanobodies were released inside the tumor and bonded with the CD47, deactivating them.
No longer having the paralyzing effect of this protein-shield, the immune system rediscovered the ability to forcefully fight the cancer. But that’s not all: the presence of fragments of the dead bacteria further attracted the body’s macrophages, thus also strengthening the defence system.
In reality, a small number of bacteria did not follow the “instructions” for the apoptosis and therefore continued to duplicate, producing – in any case – new nanobodies and reinforcing the effects of the therapy. The final result was a drastic reduction in the size of tumors, the elimination of metastases and the prolonging of the survival of the animals. Seeing that the CD47 protein is produced by many types of tumors, the researchers believe that this new form of immunotherapy may have a broad spectrum of application, if the data obtained in animals is also confirmed in humans. New studies will be undertaken in the following months.
