ARCHIVED - Vaccine stays around, causes tumours to shrink

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September 01, 2010

A new oil-based solution for delivering vaccines could pave the way for effective vaccines against cancer. In fact, one experimental anti-cancer treatment delivered by the solution has been shown to shrink tumours in mice, and is now in its first clinical trials in human cancer patients.

The vaccine technology, called DepoVaxTM, was developed by Halifax biotech company Immunovaccine (IMV). NRC researchers are helping determine just what it does and how it works.

DepoVax consists of a biologically friendly mineral oil containing liposomes — tiny spheres made of the same material as a cell membrane. These spheres are filled with material that helps the immune system recognize a foreign biological agent, said Dr. Marc Mansour, Vice President of Research and Development at IMV.

The most advanced vaccine being tested using the DepoVax technology is a new anti-cancer vaccine that is now undergoing a clinical trial in patients with prostate, breast or ovarian cancers.

Images (a) and (b) above show cross sections of the abdomens of two different mice. Both images were taken 35 days after each mouse had cancer cells injected just below the skin of its left lower abdomen. Image (a) is of a mouse that received no vaccine. The tumour is shown in green, and nearby lymph nodes are swollen (the swelling is common with active cancer). Image (b) is of a mouse 30 days after receiving the DepoVax vaccine (which was administered 5 days after the cancer cells were introduced). In the image (b) mouse, a tumour had formed and peaked in size after 2 weeks, then rapidly shrank. There is no tumour visible and the lymph nodes are not swollen. A small amount of the vaccine is still present on the right side of the animal just below the skin and fat layer.

Images (a) and (b) above show cross sections of the abdomens of two different mice. Both images were taken 35 days after each mouse had cancer cells injected just below the skin of its left lower abdomen. Image (a) is of a mouse that received no vaccine. The tumour is shown in green, and nearby lymph nodes are swollen (the swelling is common with active cancer). Image (b) is of a mouse 30 days after receiving the DepoVax vaccine (which was administered 5 days after the cancer cells were introduced). In the image (b) mouse, a tumour had formed and peaked in size after 2 weeks, then rapidly shrank. There is no tumour visible and the lymph nodes are not swollen. A small amount of the vaccine is still present on the right side of the animal just below the skin and fat layer.

A vaccine with staying power

Generally, vaccines work by teaching the immune system to recognize a particular organism and fight it off. They do this by presenting an antigen to specialized cells in the immune system (an antigen is a molecule on the surface of an organism that can be used to identify it). Anti-cancer vaccines are designed to stimulate the immune system to attack cancer cells.

Normally, vaccines are carried in solutions that are quickly dispersed by the body shortly after injection. For this reason, anti-cancer vaccines don't usually stick around long enough to effectively teach the body's immune system to fight off tumour cells, said Dr. Chris Bowen, a biophysicist at the NRC Institute for Biodiagnostics in Halifax. However, it can take weeks for the body to break down DepoVax — which represents its main advantage.

"The idea of a technology that causes vaccines to stay around longer is exciting because it means vaccines could become more effective," said Dr. Bowen. He is part of the NRC team working with IMV to observe the action of the vaccine against tumours in mice, with the help of a small-animal magnetic resonance imaging (MRI) machine located at NRC.

So far, the researchers have completed a series of studies comparing various groups of mice with tumours — some of which received a DepoVax anti-cancer treatment, and others that received no vaccine. MRI images showed that in mice given the vaccine, tumours not only shrank over time, but also disappeared.

Results are easier to see

Because of the oil-based nature of the vaccine, the vaccine itself can be seen in the MRI images, allowing researchers to observe just how long it stayed in place after it was injected. They show that the vaccine stayed at the injection site for several weeks while it gradually dissipated.

"Usually it's quite hard to see a vaccine with MRI," Dr. Bowen said. "In this case, we can look at its distribution and see what it does over time, which is very helpful for understanding the drug's action in the body." On an MRI, the vaccine appears as spots that are brighter than those of ordinary fat deposits in an animal.

In future studies, researchers hope to label the vaccine, as well as immune cells that respond to the vaccine, with iron oxide so even more details can be observed via MRI. Iron oxide has strong effects on MRI contrast. By labelling a vaccine with iron-oxide, researchers can look at MRI images and see not only where the vaccine goes but also how it affects cells.

NRC's small-animal MRI has been vital to studying in greater detail how the vaccine works and how it affects tumours, said Dr. Mansour. "We can visualize the vaccine after it has been injected in animals. And we can do this in real time, so we don't have to sacrifice the animals," he added. "We've had a great collaboration in the past year and want to continue working with NRC scientists."

A cancer vaccine clinical trial using DepoVax was launched in March 2010 in the U.S. "All of this is very exciting to us," said Dr. Mansour. He notes that DepoVax can carry antigens for a wide variety of diseases.

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