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 The preliminary findings offered hope that the experimental
treatment could turn out to be more effective than existing cancer
therapies for some inoperable tumors such as those of the lung,
breast, and pancreas, which often fail to respond to radiation and
chemotherapy.
Radiation requires oxygen to kill cells, but the deep interior of
tumors is nearly oxygen-free. Chemotherapy requires blood vessels to
carry drugs into tumors, whose interiors generally lack such
plumbing.
"But these conditions make the tumors perfect for bacteria that
thrive in low-oxygen environments," said oncologist Shibin Zhou of
the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in
Baltimore, Maryland, a senior author of the study.
Doctors first tried using streptococcus bacteria to attack tumors
100 years ago, but that and recent attempts with salmonella proved
to be toxic, ineffective, or both.
The idea nevertheless made sense, and a decade ago Hopkins
scientists resurrected the approach using Clostridium novyi soil
bacteria. They genetically modified the bug by removing DNA that
makes a toxic protein, and decided to inject only spores, which are
less likely to cause infection.
They then enlisted veterinary oncologists at seven pet clinics
across the United States. Sixteen dogs, from a border collie to
golden retrievers and shepherds, received injections of 100 million
clostridium spores.
The scientists chose dogs rather than common lab animals because
their cancers are more genetically similar to humans', potentially
making the results more relevant.
Tumors shrank in three of the 16 dogs, and disappeared in three
more, the researchers reported in Science Translational Medicine.
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At M.D. Anderson Cancer Center in Houston, a patient with
retroperitoneal leiomyosarcoma, an aggressive cancer of the abdomen
that had spread to her liver, lungs, bones, and arm, received an
injection of 10,000 spores into a metastatic tumor in her arm. She
initially ran a fever and felt severe pain (a sign that her immune
system was attacking the cancer) but the tumor shrank in and around
her arm bone. Tumors elsewhere continued to grow.
What seems to happen, Zhou said, is that the spores release enzymes
that destroy nearby tumor cells "so precisely we call it biosurgery."
Also, the immune system senses the bacteria and dispatches
tumor-killing cells.
BioMed Valley Discoveries, a research and development company in
Kansas City, Missouri, is recruiting patients with solid tumors that
have not responded to therapy for a trial assessing the safety and
optimal dose of clostridium, at M.D. Anderson and other sites. "We
anticipate that proceeding through Phase 1 and future later-stage
trials will take many years," said BioMed's Saurabh Saha.
(Reporting by Sharon Begley; Editing by James Dalgleish)
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