What Do You Get When You Combine a Tumour-Eating Clostridium Bacteria with Liposome Packaged Doxorubicin and Irinotecan? More Dead Tumour Cells

Scientists at Johns Hopkins Kimmel Cancer Center have been using Clostridium Novyi against tumours in mice for over five years now. But by combining genetically modified C. Novyi-CT with liposome confined chemotherapy agents Doxorubicin and Irinotecan, the scientists learned how to kill even more of the tumour cells.

Combining C.novyi-NT and liposomes filled with chemotherapy seems to have its synergistic effect on tumors owing to the presence of an enzyme found lurking in C. novyi-NT cultures, which Ian Cheong, Ph.D., in the Vogelstein lab dubbed liposomase. It destroys fatty membranes and may disrupt the outer layer of liposomes releasing their drug contents.

“Drugs contained in these ‘Trojan horse’ compartments are specifically released at the tumor site by the C-novyi-NT bacteria which may improve the effectiveness and safety of the therapy,” says Cheong who is the lead author of the study.

The scientists note that liposomase could be used in a variety of other targeted therapies besides the bacteria combination. Such approaches could include attaching liposomase to antibodies that have an affinity for specific tumors or adding its DNA code to gene therapy. As many drugs can be packaged within liposomes, the investigators say the approach could have general utility.

In a companion study published in the November 19 online issue of Nature Biotechnology, the Hopkins team decoded the entire C.novyi-NT genome which Zhou says “was instrumental in identifying liposomase and will help improve our bacterial-based therapies.”

Preliminary safety tests of injected C. novyi-NT alone are under way in a small number of cancer patients.

....The likely explanation for the greater cancer cell kill by the combination treatment is that the bacteria expose the tumors to six times the amount of chemotherapy than is usually the case by improving the breakdown and dispersal of the chemotherapy’s fatty package at the tumor site.

The investigators repeated experiments using two packaged chemotherapy drugs -- doxorubicin and irinotecan -- and observed similar tumor-killing effects of both when used in combination with the bacteria.

“Packaged” cancer drugs currently are available in microscopic fatty capsules called liposomes which gravitate to tumors because they are too large to fit through the skins of tightly-woven blood vessels surrounding normal tissue and small enough to get through tumor vasculature.

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Using bacteria and viruses against tumours is a biological form of nanotechnology medicine. It is actually the enzymes and other nano-sized molecular machines that assist human scientists in killing the tumours. Eventually scientists will learn to make improved versions of these nano-machines. For now, it is nice to be able to use the deadly spore-forming bacteria as a force for life.