FAMRI-Funded Research Helps Harness Cancer-Killing Viruses

SPARS Manages FAMRI Peer Review

The not-for-profit foundation, Flight Attendant Medical Research Institute (FAMRI; http://www.famri.org), sponsors scientific and medical research to combat the diseases caused by exposure to tobacco smoke.

Since 2001, the foundation has relied on SPARS to manage large- and small-conference peer review meetings that have marshaled the wide-ranging expertise of hundreds of reviewers and funded nearly 500 projects addressing the prevention, early detection, treatment, and cure of diseases and medical conditions caused by tobacco smoke.

FAMRI Research Harnesses Viruses to Kill Cancer

Diffused within healthy cells, especially at early stages, and growing out of control, cancer cells are difficult to target precisely. As a result, traditional anticancer therapies are blunt instruments: chemotherapy can affect fast-growing but healthy cells like bone marrow, hair, and skin; radiation cannot always focus precisely; lumpectomies may miss malignant or premalignant tissue.

But, in a series of elegant and innovative FAMRI-funded studies, Dr. Yuman Fong of Memorial Sloan-Kettering Cancer Center is harnessing the propensity of viruses to cause cell death, and aiming that propensity at cancer cells. He is designing viruses that selectively infect tumor cells and can kill them within hours.

A virus's strategy is to capture a cell's replicating machinery, producing thousands of viruses until the infected cell bursts, or lyses, releasing the newly made viruses, and spreading infection. A cancer cell is a virus's perfect target - its replicating machinery is out of control - it has no protective 'off' switch. Dr. Fong's laboratory focuses on engineering viruses (herpes simplex 2, adeno, vaccinia, myxoma, and vesicular stomatitis) that specifically infect and lyse cancer cells (oncolytic viruses), while sparing normal cells.

In a FAMRI-supported 2004 study, the investigators used a herpes simplex virus called NV1066 that they engineered to contain a gene for a protein called "green fluorescent protein" (GFP). They wanted to use the modified virus to infect early cancer cells and cancer cells in hard-to-reach tissues like nerves. It did just that, and only the cancer cells with the GFP glowed green.

These experiments showed that viruses can be used to improve early detection and identification of cancer, and to help guide surgical resection. "In animal and in human studies, they [the viruses] have been able to detect one tumor cell in a background of one million normal cells, a 50 times improvement over traditional cytology)," writes the PI.

This work has global ramifications. The investigators in Dr. Fong's lab point out that using this technique, the cancer cells that become virus-tagged and glow green under the appropriate light source can be seen by personnel with minimal training using available, inexpensive machines. Dr. Fong suggests that these qualities may make the techniques appropriate "even in rural areas of developing nations where cigarette smoking is still popular..." allowing detection of many types of cancers including lung, oral, pancreatic, and stomach, and could be immediately applicable worldwide.

Steadily building on the success of previous work, another FAMRI-supported study by Fong et al., in 2007, continued this work, with an added twist. They asked, "What cellular change in the process of malignant transformation allows the virus to selectively infect the cancer cell?"

Dr. Fong and colleagues have carried out a great deal of FAMRI-funded research; they have been working steadily since 2004 to develop oncolytic viral therapies, some of which are now entering Phase 1 clinical trials.