Researchers at the University of Cincinnati have developed a similar strategy for cancer treatment by linking cancer cells with powerful radiation therapy to bacteria acting as an adapter. The study’s findings were published in Advanced Healthcare Materials.
Basics of radionuclide therapy
This treatment is typically delivered in a targeted manner, with cancer-killing radiation binding to cancer cells via receptors on the cell surface to spare as many surrounding healthy cells as possible.
Kotagiri, a University of Cincinnati Cancer Center researcher and associate professor at UC’s James L says “Each type of cancer has its own unique epitopes, or receptors, that are expressed on its surface, you can deliver medicine or radiation using molecules such as antibodies and peptides only to the cancer cells where it needs to go, and not anywhere else, such as vital organs.”
Targeted therapy using conventional strategies can be effective, but cancer cells can mutate so that the receptors are no longer on the surface and the radioactive material has nothing to bind to. This leads to resistance to treatment and the treatment may also be ineffective for other patients because they never had the receptors present on their cancer cells to begin with.
Bacterial adapters
Kotagiri said probiotic bacteria can be helpful and are different from bacteria that cause disease. Although the bacteria are harmless to cancer, they tend to collect inside tumors because they provide a low-oxygen, immunocompromised environment where the bacteria thrive.
The research team engineered a unique strain of probiotic bacteria that overexpresses a unique transporter that binds and concentrates metals, especially copper, inside the bacteria. This process is facilitated by molecules known as siderophores, which bind to metals.
Since the radionuclide is made of copper, the siderophore molecule latches on to it, creating a targeting agent that then binds to the bacterial transporter similar to how antibodies bind to other receptors for traditional targeted therapy.
In essence, engineered bacteria provide artificial receptors for a target substance inside tumors that can be effectively used as adapters in any type of tumor, regardless of the tumor’s receptor profile. The bacteria itself is highly resistant to radiation, but through a process known as the bystander effect, the radionuclide destroys nearby cancer cells once it concentrates inside the bacteria.
“As long as these engineered bacteria are inside the tumor, these bacteria-specific targeting agents will transport the radioactive metal,” Kotagiri said. “They won’t care if there is a cancer cell that expresses the receptor or not. All they care about is that they’ve identified something they can recognize, accumulate and keep.”
The ability of the engineered bacteria to maintain their population inside tumors exclusively means that the bacteria need not be administered more than once.
“So we can make this transition between copper-64 and copper-67 smoothly to image the tumor, and after we’ve imaged, we can reintroduce another molecule to do the therapy,” Kotagiri said. “We wanted to show that it was possible to use the same kind of technology that was previously used to image infections for cancer treatment.”
As research into bacteria-based therapies continues, Kotagiri said one hurdle will be gaining wider acceptance in the medical community that the approach is safe. Further research will also need to confirm that the bacteria naturally and exclusively colonize inside tumors when they enter the bloodstream.
Once a general consensus on safety is reached, Kotagiri envisions this therapeutic approach being tested in human clinical trials first in situations where the bacteria can be directly injected into tumors that are resistant and where no other receptors or therapies are available.
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