This archive report was first published on 4 July 2019.
New Cancer Treatment: Genetically Reprogrammed Bacteria ¶
Published on July 4, 2019, in the journal Nature Medicine, a groundbreaking study has demonstrated the potential of genetically reprogrammed bacteria to destroy tumors in mice.
Researchers at Columbia University and Massachusetts General Hospital have been working on a novel approach to cancer treatment, using bacteria to turn the immune system against cancer cells. The innovative method involves genetically reprogramming bacteria to produce nanobodies, which are small, potent molecules that can attach to CD47 proteins on cancer cells, masking their 'Don't Eat Me' sign.
Ordinary bacteria will colonize tumors in the body, using them as a refuge from the immune system. In 2016, Dr. Tal Danino helped construct bacteria that can make drugs to fight tumors after entering them. The researchers inserted the nanobody gene into the bacteria, turning them into nanobody factories.
The team injected five million of the altered microbes into mouse tumors. The bacteria were programmed to commit mass suicide, spilling out nanobodies that attached to CD47 proteins on the cancer cells, robbing them of their camouflage. Fragments of the dead bacteria leaked out of the tumor, drawing the attention of immune cells, which attacked the uncloaked cancer cells.
Inside the besieged tumor, the surviving bacteria started multiplying again. When the population grew large enough, the majority committed suicide once more, delivering another pulse of nanobodies and fragments. The double-whammy may eliminate the tumors into which the bacteria were injected.
Dr. Michael Dougan, an immunologist at Massachusetts General Hospital, said, 'I love it when this kind of thing happens. It's a great little machine.'
The approach has the potential to reduce the side effects of cancer treatment, as the bacteria coordinate targeted attacks on the tumors, and the nanobodies that leaked from the cancer cells are quickly cleared by the body.
Dr. Nicholas Arpaia and his colleagues reported an additional benefit. After they killed off one tumor with bacteria, other tumors in the mice also shrank, suggesting that the bacteria helped the immune system learn to recognize other cancer cells.
Dr. Danino co-founded a company, GenCirq, that is exploring using these reprogrammed bacteria to treat cancer. Dr. Arpaia is on the leadership board. Their goal is to treat some forms of metastatic cancer with a pill of programmed bacteria.
Dr. Tim Lu, a computational biologist at M.I.T., said, 'These things are not just seen as crazy things to play with. They potentially could actually make their way into patients.'
