Cancer patients regularly have to undergo a form of treatment called immunotherapy, which is meant to boost the immune system and help the body find and destroy cancerous cells. The way it is performed is through an intravenous infusion exclusively at a medical facility. This can happen monthly, weekly, or even daily. But in the future, cancer patients could perform immunotherapy by themselves, at home or while traveling, just by popping a pill.
At least, that’s the dream of researchers at Tel Aviv University who’ve just published a promising new study that describes synthetic molecule-based immunotherapy in pill form. If proven successful in humans, it would mark the first pill-form immunotherapy for cancer.
How immunotherapy works
True to its name, immunotherapy is all about using our immune system to fight cancer cells, which are typically hard to detect and target for destruction.
Because cancer cells actually start as normal cells, the immune system doesn’t always recognize them as foreign. Indeed, many people end up getting cancer although their immune system is perfectly healthy. But with an injection of certain antibodies, the immune system can be primed to have a fighting chance at detecting these rogue cells, thereby improving patient outcomes without the severe side effects associated with chemotherapy.
This therapy proved so revolutionary when it was first introduced in the 1980s that James Allison and Tasuku Honjo, who both discovered proteins that activated the immune system against cancer, were awarded the 2018 Nobel Prize in Medicine.
The problem is that antibodies cannot survive the highly acidic environment of the human gut, which is why attempts at developing immunotherapy for cancer in a pill form have fallen short.
But researchers in Israel led by professor Ronit Sacthi-Fainaro, the head of Tel Aviv University’s Center for Cancer Biology Research, think they’ve found a promising lead. They’ve developed a synthetic molecule, after reviewing thousands of candidates, that mimics one of the most common immunotherapies, stopping two proteins (PD-1 and PD-L1) from suppressing the immune system. Most importantly, this synthetic molecule looks like it can withstand absorption through the human intestines without being broken down.
“This is important, as the new molecules have many advantages. They can be given orally, are cheaper to produce than antibodies, and penetrate more areas of the tumor than antibodies can reach,” Satchi-Fainaro told The Times of Israel.
Additionally, the synthetic molecules are nearly 300 times smaller than conventional antibodies. Because they’re so large, typical antibodies need to be carried through blood vessels to move around, but some cancer cells may be located far away from blood vessels and could thus escape the immune system more easily.
Since they’re much smaller, the synthetic molecules developed by the researchers in Israel could thus travel to tumors that would typically be out of reach and trigger an immune response, while being more resistant to degradation in the gut. Conventional immunotherapy has a success rate of around 15%, which may get a hefty bump if the stars align and this new synthetic molecule actually works as intended in human patients.
“If there are fewer blood vessels in a particular area of the tumor, the antibody will not be able to get inside. The small molecule, on the other hand, diffuses, and is therefore not entirely dependent on the tumor’s blood vessels or on its hyperpermeability. I believe that in the future, the small molecule will be commercially available and will make immunotherapy affordable for cancer patients,” said Prof. Satchi-Fainaro.
But by far the new molecule’s biggest advance over antibody immunotherapy is cost. Because they’re biological, producing antibodies requires a complex infrastructure and specialized staff. It costs around $200,000 per year per patient to make a full course antibody treatment, which is obviously out of reach for most people. In contrast, the synthesized version of this therapy can be produced in a shorter time and at a fraction of the cost.
At the moment, it has been tested in vitro and on a human tumor in a special lab model. These tests confirmed the molecule controlled tumor growth as effectively as PD-L1 in animals. The hardest test is yet to come, though. It may be years before we see clinical trials for this novel treatment, but the wait may be well worth it.
The findings were reported in the Journal for ImmunoTherapy of Cancer.