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Genetically modified cells attack tumors

sociate member of Molecular Pharmacology at St. Jude. Therefore, the study holds special promise for children with high-risk neuroblastoma because as many as 80 percent of these patients relapse with chemotherapy-resistant metastatic cancer. Neuroblastoma is considered high risk if the tumors have certain genetic mutations or have already spread when the cancer is diagnosed.

"Clinicians are limited in how aggressively they can treat these children because the chemotherapy drugs produce harsh side effects and therefore must be administered at reduced levels," Danks said. "But by targeting tumor cells while avoiding normal cells, doctors could treat the neuroblastoma aggressively while minimizing side effects." Danks is senior author of the PLoS ONE report.

The researchers based their new treatment on work previously reported that showed certain NSPCs have a natural tendency to seek out damaged or cancerous areas in the brain.

In the current study, the researchers first injected into mice that had neuroblastoma large numbers of NSPCs that had been genetically modified to carry a drug-activating enzyme called rabbit carboxylesterase (rCE). The NSPCs traveled to the tumors and used the gene to produce rCE. Three days later the team injected the CPT-11 into the mice. The drug dispersed throughout the mice but was activated by rCE selectively at the neuroblastoma tumors. The researchers used the rabbit form of this enzyme because it activates CPT-11 much more efficiently than the human version, Danks said. This activation is essential to treatment because the activated form is up to 1,000 times more active than CPT-11.

While half of a group of 10 mice that received only CPT-11 survived for six months, all 10 mice treated with both the modified NSPCs and CPT-11 survived for more than six months.

"There is a real need for new treatments for neuroblastoma that target tumor cells while having minimal side effects," said
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Contact: Summer Freeman
summer.freeman@stjude.org
901-495-3061
St. Jude Children's Research Hospital
21-Dec-2006


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