Engineering an “Invisible Cloak” for Bacteria to Deliver Cancer Drugs

Scientists exploring a novel but highly promising avenue of cancer treatment have developed a type of “invisibility cloak” that helps engineered bacteria sneak through the body’s immune defenses. The result is more powerful delivery of anti-cancer drugs and shrinking of tumors in mice, with the scientists hopeful the approach can overcome toxicity issues that have plagued these techniques so far.

Traditional forms of cancer treatment – radiotherapy, chemotherapy and immunotherapy – each have their own strengths when it comes to combating tumors, and what’s known as therapeutic bacteria could bring its own set of skills into the mix. Bacteria itself can have powerful anti-tumor effects, but genetic engineering could allow it to take on entirely new capabilities, including releasing specific compounds or carrying potent anti-cancer drugs. There are a number of challenges in using bacteria for this purpose, however, with the issue of toxicity chief among them. Living bacteria can grow rapidly in the body, and because the body’s immune system sees them as a threat, too many can trigger an extreme inflammatory response.

In clinical trials, these toxicities have been shown to be the critical problem, limiting the amount we can dose bacteria and compromising efficacy,” said Columbia University‘s Jaeseung Hahn, who co-led the research. “Some trials had to be terminated due to severe toxicity.

Addressing this toxicity problem would mean finding (or engineering) bacteria that can evade the body’s immune system and safely make it to a tumor to fulfill their anti-cancer potential. Hahn’s team has made new inroads in this space by turning to sugar polymers called capsular polysaccharides (CAP), which naturally coat bacterial surfaces and protect them from immune attacks.

We hijacked the CAP system of a probiotic E. coli strain Nissle 1917,” said Tetsuhiro Harimoto, the study’s co-lead author. “With CAP, these bacteria can temporarily evade immune attack; without CAP, they lose their encapsulation protection and can be cleared out in the body. So we decided to try to build an effective on/off switch.”

Source: https://www.engineering.columbia.edu/

How to Destroy Cancer by Training Immune Cells

While it sounds like the stuff of science fiction, a cancer treatment in which a patient’s own cells are engineered to hunt down and wipe out their disease — and then linger in the body to stop the cancer returning — is helping to save patients’ lives. The results of the treatment, known as CAR T-cell therapy, have been astonishingPatients who had exhausted all other options and been told they had just months to live have gone into remission. Others have even been cured by the one-off dose.

In trials, all signs of cancer disappeared in more than 80 per cent of patients with acute lymphoblastic leukaemia — the most common cancer in children — after receiving CAR T-cellsSuccess stories include Emily Whitehead, now 16, who in 2012 became the first child in the world to take part in a CAR T-cell trial. Emily, who only had weeks to live when her leukaemia became resistant to conventional therapies, had the revolutionary treatment at the Children’s Hospital of Philadelphia in the U.S. when she was six years old. She is still cancer-free today.

First given in the NHS two years ago to children with a rare blood cancer, CAR T-cell therapy is now used to treat four forms of the disease — and more could follow. It is also being trialled in a number of other blood cancers, such as myeloma, non-Hodgkin lymphoma and chronic lymphocytic leukaemia, and could be available soon for these patients. Early research suggests it can also tackle solid tumours. A new study showed that a new generation of CAR T-cells with more advanced genetic engineering could help treat mesothelioma, ovarian cancer and the deadly brain cancer glioblastoma in mice, without side-effects, reported the journal Science Translational Medicine.

The current uses of CAR T-cell therapy are ‘just the tip of the iceberg’, says Dr Andrew Furness, a consultant medical oncologist at the Royal Marsden Hospital in London. ‘Doctors and scientists are working tirelessly to expand its reach to many more patients.’

CAR T-cell therapy (or chimeric antigen receptor T-cell therapy) is a form of immunotherapy, using the power of a patient’s immune system to fight the disease.

Source: https://www.dailymail.co.uk/