Researchers from Columbia University have developed a novel gene therapy technique that uses a virus engineered to replicate only within cancer cells and produce a protein toxic to those cells. The results of their laboratory studies, presented at the 2007 AACR annual meeting, showed complete eradication of both primary and distant tumors in a mouse model of prostate cancer.

The investigators built their system around a gene called mda-7/IL-24, which produces the cytokine IL-24, a signaling protein important to the immune response, that kills cancer cells when expressed at high levels. They engineered an adenovirus carrier for the gene, which can multiply within cancer cells. The virus was altered to replicate in response to transcription factors found only in cancer cells. When the virus enters a cancer cell, the researchers explained, it replicates millions of copies of itself and produces IL-24, which kills the cell and releases a flood of virus into the bloodstream to infect and kill other cancer cells.

After in vitro experiments confirmed that viral replication was confined to cancer cells and induced growth inhibition and cell death, the investigators tested their gene therapy system in a xenograft mouse model of therapy-resistant prostate cancer. The virus completely eradicated not only the primary tumor but also distant tumors, explained the study's leader, Dr. Devanand Sarkar from Columbia University.

An earlier version of the therapy has already been tested in a phase I clinical trial, producing a significant clinical response in several of the patients who completed one 28-day treatment cycle. Experiments to test the next-generation treatment in mice with fully functional immune systems are ongoing, Dr. Sarkar said.