Homing In on Tumors

24 March 2006 (All day)

Thorne et al., Science

On target.
When the vaccinia virus was delivered in CIK cells, it was evenly distributed throughout the tumor (left). For virus delivered alone however, distribution was uneven (right).

Researchers have eliminated metastatic cancer in mice by combining the two best candidates yet in a new technique that packs a one-two punch. The result--still a preliminary finding--illustrates the potential for improved cancer treatment through saddling a cancer-killing virus on the back of a tumor-targeting immune cell.

Most current cancer treatments, such as chemotherapy, can't tell healthy cells from cancerous ones. Therapies based on immune cells, which target particular tumor molecules, are more specific, but they are not effective against a variety of tumors. As a result, cancer biologists have turned to a new strategy, known as targeted biological therapy, in which cancer-killing viruses are combined with immune cells. Once the immune cell latches onto a tumor, the virus bursts out and destroys the cancer cells. Finding an immune cell that targets a whole host of tumors and a virus that doesn't release too early, however, has been a challenge.

Now virologists at Stanford University led by Steve Thorne and Christopher Contag have met that challenge by finding the best candidates for the job. First, they identified a type of immune cell, known as a cytokine-induced killer (CIK), that has a taste for many kinds of tumors. Then, for the cargo, they chose the vaccinia virus. Long used as a vaccine for smallpox, vaccinia patiently waits up to 72 hours before busting out. That's enough time for the immune cells to find even the most hidden tumor. In other immune cells, vaccinia goes pop in as little as 4 hours. The team's system has another advantage: CIK cells burrow deep into tumor tissue; that means the virus shouldn't harm surrounding healthy cells.

When the researchers tried the system out in cancer-ridden mice, the CIK cells shot straight for the tumors. Two days after injection, vaccinia was replicating deep inside the tumors and was barely detectable in other parts of the body, the team reports today in Science. Of the eight mice that received this therapy, all completely recovered from their tumors. In a separate group of mice, injecting CIK sans virus only prolonged survival for an extra week; virus alone cured just two out of eight mice tested. That's still a small sample, but this is the first time researchers have managed to create a system like this that works in a clinically relevant setting.

"This is an excellent example of how combination cancer therapies can have additive effects," says Inder Verma, a geneticist at The Salk Institute in San Diego, California. "I think this is the way of future cancer treatments." Even though the Stanford team believes that the vaccinia viruses and the CIK cells are the best available right now, "it is possible that further investigation will produce improvements on this system," says Contag.

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