Genetically Engineered Anaerobic Bacterium Controls Pancreatic Tumors in Mice

Intravenous injection of a genetically engineered strain of Clostridium perfringens (Cp) prolongs tumor-free survival in mice with pancreatic cancer.  The internal region of tumors often lacks oxygen and is less responsive to some therapies. To attack that hypoxic core, researchers have tried injecting tumor-bearing mice with anaerobic bacteria, such as Cp, that thrive in oxygen-depleted environments. However, wild-type Cp retains the ability to grow in the presence of oxygen and led to toxic effects in other tissues making it unsuitable for anti-cancer therapy.

In the current study, Savio Woo, Ph.D., of the Mount Sinai School of Medicine in New York and colleagues deleted a key oxygen tolerance gene (sod) from the bacterial genome. They also introduced a gene, PVL, from the bacterium Staphylococcus aureus that evades inflammatory responses in the host. They tested the anti-tumor activity of the Cp/sod-/PVL bacteria by injecting it intravenously into mice that had pancreatic tumors.

Mice injected with Cp/sod- bacteria had fewer toxic effects than those injected with wild-type Cp. Moreover, mice treated with the Cp/sod-/PVL bacteria had fewer inflammatory cells in the tumor site than those injected with either the wild-type or Cp/sod- bacteria. The median tumor-free survival for animals injected with the Cp/sod-/PVL bacteria was 77 days - and approximately half of the animals became long-term survivors - compared with 30 days and no long-term survivors for those treated with the Cp/sod- bacteria.

"Taken together, this newly constructed bacterial strain, Cp/sod-/PVL, has substantially elevated tumor selectivity and onco¬pathic potency. These improvements may lead to the development of safe and effective oncopathic agents for the treatment of patients with pancreatic cancer and other poorly vascularized tumors in the future," the authors conclude.  Contact: Lauren Woods