Tumor-targeting viral therapy slows neuroblastoma, malignant peripheral nerve sheath tumors

Study led by Cincinnati Children's suggests innovative therapy for hard-to-treat solid tumors

CINCINNATI –Researchers in a multi-institutional study led by Cincinnati Children’s Hospital Medical Center slowed the growth of two particularly stubborn solid tumor cancers – neuroblastoma and peripheral nerve sheath tumors –without harming healthy tissues by inserting instructions to inhibit tissue growth into an engineered virus, according to study results published in the February 15 Cancer Research.

“Malignant solid tumors are still very difficult to treat effectively, especially without causing harm to normal tissues, so we need to find innovative therapeutic approaches,” said Timothy Cripe, M.D., Ph.D., a physician and researcher at Cincinnati Children’s. “In our study, this tumor-targeting viral therapy enhanced anti-tumor activity by stimulating multiple biological processes, including directly killing the cancer cells and reducing the formation of blood vessels that fed the tumors. These data support continuing development and study of our tumor-targeted viral therapy to fight cancer.”

Previous research has documented that oncolytic herpes simplex virus (oHSV) and similar viruses can infect and kill human cancer cells without harming normal, healthy cells or causing disease. In their study, Dr. Cripe and his colleagues genetically armed oHSV with a gene that carries instructions for a cancer-fighting protein, human tissue inhibitor of metalloproteinase 3 (TIMP3). TIMP3 blocks enzymes that aid the development and progression of cancer, called matrix of metalloproteinases (MMP). Specifically, MMPs help break down molecules that are important for the structural support and normal development of cells, organs and maintenance of tissues. When MMP activity becomes unbalanced, the enzyme plays a well-documented role in the formation of invasive and metastatic cancers, including pediatric neuroblastoma, the most common solid cancer tumor in childhood.

Researchers dubbed the tumor-targeted viral therapy created by combining of TIMP and oHSV as rQT3. In laboratory studies involving human cancer cells and mice designed to develop neuroblastoma or peripheral nerve sheath tumors, rQT3 reduced new blood vessel development and increased toxicity to both kinds of tumor cells. In addition, rQT3 treatment resulted in longer life spans in mice compared to mouse models receiving just saline or other treatments.

Dr. Cripe said the researchers also discovered that rQT3 reduced the number of circulating endothelial progenitors (CEP). CEPs are derived from blood marrow and circulate in the blood. They have the ability to become cells that line blood vessels to promote blood flow.