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.
“Our findings suggest that therapeutic viruses can act systemically by limiting the mobilization and recruitment of bone-barrow derived progenitors, both CEPs and others, that contribute to the tumor microenvironment and growth, resulting in the restriction of new blood vessel growth that can feed tumors,” Dr. Cripe said.
Neuroblastoma is a solid tumor cancer that begins in the sympathetic nervous system and most often strikes children younger than 5 years old. For children younger than 2, or those with a single mass tumor, the combination of surgery and chemotherapy has led to cure rates of 90 to 95 percent. In older children or those with metastatic disease, neuroblastoma is a much harder to fight. Tumor cells are often able to survive ordinary doses of chemotherapy and radiation, leading to relapses that are difficult to cure. During the last three decades, Cincinnati Children’s has been a leader in developing high-dose chemotherapy used in combination with bone marrow transplants and other drug treatments to help improve outcomes for patients with high-risk neuroblastoma. Malignant peripheral nerve sheath tumors are cancers affecting the connective tissue surrounding nerves. The first-line treatment is surgical removal with chemotherapy or radiotherapy used as auxiliary therapies.
Nick Miller | EurekAlert!
Self-organising system enables motile cells to form complex search pattern
07.05.2019 | Westfälische Wilhelms-Universität Münster
Mouse studies show minimally invasive route can accurately administer drugs to brain
02.05.2019 | Johns Hopkins Medicine
The quality of additively manufactured components depends not only on the manufacturing process, but also on the inline process control. The process control ensures a reliable coating process because it detects deviations from the target geometry immediately. At LASER World of PHOTONICS 2019, the Fraunhofer Institute for Laser Technology ILT will be demonstrating how well bi-directional sensor technology can already be used for Laser Material Deposition (LMD) in combination with commercial optics at booth A2.431.
Fraunhofer ILT has been developing optical sensor technology specifically for production measurement technology for around 10 years. In particular, its »bd-1«...
The well-known representation of chemical elements is just one example of how objects can be arranged and classified
The periodic table of elements that most chemistry books depict is only one special case. This tabular overview of the chemical elements, which goes back to...
Light can be used not only to measure materials’ properties, but also to change them. Especially interesting are those cases in which the function of a material can be modified, such as its ability to conduct electricity or to store information in its magnetic state. A team led by Andrea Cavalleri from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg used terahertz frequency light pulses to transform a non-ferroelectric material into a ferroelectric one.
Ferroelectricity is a state in which the constituent lattice “looks” in one specific direction, forming a macroscopic electrical polarisation. The ability to...
Researchers at TU Graz calculate the most accurate gravity field determination of the Earth using 1.16 billion satellite measurements. This yields valuable knowledge for climate research.
The Earth’s gravity fluctuates from place to place. Geodesists use this phenomenon to observe geodynamic and climatological processes. Using...
Discovery by Brazilian and US researchers could change the classification of two species, which appear more akin to jellyfish than was thought.
The tube anemone Isarachnanthus nocturnus is only 15 cm long but has the largest mitochondrial genome of any animal sequenced to date, with 80,923 base pairs....
29.04.2019 | Event News
17.04.2019 | Event News
15.04.2019 | Event News
19.06.2019 | Physics and Astronomy
19.06.2019 | Information Technology
19.06.2019 | Materials Sciences