Clostridium novyi bacteria. Credit: CDC
A new mouse study at the Johns Hopkins Kimmel Cancer Center demonstrates that combining liposome-encapsulated chemotherapy drugs with bacterial therapy dramatically improves the prospects for cancer eradication.
Reported in the Nov. 24 issue of Science, Hopkins researchers demonstrated that the genetically-modified bacteria Clostridium novyi-NT (C. novyi-NT) thrive in oxygen-starved environments like those found inside cancer cell clusters and can be targeted to disrupt cell membranes and destroy cancer tumors.
“It is not difficult to kill cancer cells,“ says Bert Vogelstein, MD, professor and co-director of the Ludwig Center and Howard Hughes Medical Institute at the Johns Hopkins Kimmel Center. “The challenge is in killing them while sparing normal cells.“
The bacteria’s cancer-killing effects were first discovered five years ago by the Hopkins team, who noticed the bacteria’s ability to grow and spread in the oxygen-poor core of mouse tumors and the blackened scars signaling that most of the cancer cells had been destroyed. Normal surrounding cells were largely unaffected. But the bacteria failed to kill cancer cells at the oxygen-rich edge of the tumors.
In the recent study, the Hopkins team added liposome-encapsulated chemotherapy drugs to the bacterial therapy. The combo approach temporarily wiped out both large and small tumors in almost 100 mice and cured more than two-thirds of them.
The bacteria expose the tumors to six times the amount of chemotherapy than usual by improving the breakdown and dispersal of the drug at the tumor site. The bacterial factor responsible for the enhanced drug release was identified by the researchers as a previously unrecognized protein termed liposomase, which destroys fatty membranes and disrupts the outer layer of liposomes, thus releasing the drug.
The scientists note that liposomase could be used in a variety of other targeted therapies, including attaching liposomase to antibodies that have an affinity for specific tumors or adding its DNA code to gene therapy.
In a paper published online Nov. 19 in Nature Biotechnology, the Hopkins team reported the decoding of the C. novyi-NT genome.
The research was funded by the Virginia and D.K. Ludwig Fund for Cancer Research, the Commonwealth Foundation, Miracle Foundation, and the National Institutes of Health.
Co-authors include Shibin Zhou, Ian Cheong, Xin Huang, Chetan Bettegowda, Linus A. Diaz, Jr., and Kenneth W. Kinzler at Johns Hopkins.