Using microbes discovered in volcanoes, deep sea vents and glaciers to treat cancer may sound like science fiction, but Dr. Lakshmi Krishnan disagrees. She’s currently developing a cancer therapy using these microbes that could one day be used to treat melanoma and other types of cancers.

Krishnan is an immunologist with the National Research Council (NRC) in Ottawa and the Principal Investigator on a project using archaea – microbes that come from the most inhospitable environments on earth – to help the body’s immune system fight melanoma cancer cells and ultimately destroy melanoma tumours. The project recently completed a successful three-year preclinical phase, funded by the Ontario Institute for Cancer Research (OICR).

“We are certainly very happy with the results,” Krishnan says. “This is a very promising and potent candidate for treating melanoma in the future.”

Archaea are naturally some of the toughest microbes on the planet. Millions of years evolving in extreme environments have helped them develop membranes (composed of fat molecules) that withstand boiling heat, freezing cold, acids and salty wastes. This makes them unique as their fat molecules can boost the immune system of mammals, provoking extremely strong immune responses from the human body and boosting the body’s ability to fight disease.

“When we talk about ancient bacteria that live in deep sea vents,” Krishnan says, “people think we are talking about ancient stuff and get very excited by it.” She’s quick to point out that the archaea they use – termed archaeosomes – are actually grown by her team in their own lab. There, her team extracts lipids (fats) from the archaeosomes, which are then used to create therapies for use in animal models.

“Our ongoing effort is to understand the mechanisms of how these lipids work,” Krishnan says. “If we can see how each lipid does what, we can understand much more about them and create more effective treatments.”

“The use of archaeosomes to create a stronger immunological response is a novel approach to treating melanoma,” says Dr. Bob Phillips, Deputy Director of OICR. “By helping the body’s immune system destroy cancer cells on its own, it has the potential to offer a much more benign therapy to those living with melanoma.” 

One of the most important aspects of the research has been the use of archaeosomes as an adjuvant to help boost the effectiveness of a potential cancer vaccine. (Unlike the common vaccine for the flu, the vaccine Krishnan’s team is focusing on is not preventive; rather, it is used to attack cancer cells once they have already entered the body.)

Adjuvants are used in all vaccines to boost the immune system, increasing the vaccines’ effectiveness. Currently there is only one licensed adjuvant available to vaccine producers – alum.

“The big hurdle in the development of vaccines for diseases such as cancer and HIV is the ability to induce T cells,” Krishnan says. “Alum is not a very good adjuvant for T cells. If we can use archaeosomes as an adjuvant instead of alum, it will specifically induce T cells and create a more effective vaccine.”

The vaccine has been successful in lab tests. “In animal models we see a very clear increase in survival,” Krishnan says. “If we treat them with the vaccine we can delay the onset of the tumour for a month, and 20 to 30 per cent survive with no cancer at all.”

But the problem Krishnan currently faces is that the protection doesn’t last indefinitely – eventually, the cancer resurfaces.

“This is our challenge,” Krishnan says. When the cancer comes back, the T cells that originally fought the cancer off are still there – they are just no longer doing their job. Researchers initially thought the answer would be to increase the quantity of T cells, but they quickly found that didn’t work.

“You actually need not just more T cells but you need to maintain the right quality of T cells,” Krishnan explains. “We are now trying to find ways to maintain the right quality of T cells for a longer period of time to ensure that the cancer does not come back.”

Krishnan’s involvement with the project began in 1998, when she joined the NRC archaeosome team as an immunologist. “They recognized there may be some potential on the immunology side, so I was asked to move that project along.”

She has been working on a variety of projects involving the immunological potential of archaeosomes ever since, both for the University of Ottawa and the National Research Council (NRC) in Ottawa. The melanoma project has been one small but crucial part of a larger research project that began at the NRC over 25 years ago. “This is an extension of the work that has been going on a long time,” Krishnan says.

While this project focused on melanoma specifically, the team hopes that it will have wider applications as the research moves into its next phase.

“We selected melanoma because it is a great model system to use to ask questions,” Krishnan says. “The antigens are known. It is a major cancer that affects a lot of people. Therefore, we are using it as a model system for cancer. If we can get our research to work with melanoma, it is a great sign.”

Krishnan hopes that she will be able to begin clinical trials within the next five years. Eventually, she would like to see archaeosome-based vaccines helping to treat people with various forms of cancer.

“When you talk about vaccines, especially with a technology like this which is applicable to a number of things, people get very excited,” she says. “But vaccine development is a very long process. I believe that vaccines have great applications for cancer, but it takes time.”

“We are not going to stop,” Krishnan promises. “We are going to keep continuing to refine the technology. The archaeosome technology could revolutionize future cancer treatment and OICR helped us move in this direction.”