Electron Microscopy Reveals Molecular World in 3D
Although electron microscopy (EM) has been in the cell biologist’s toolkit for decades, recent technological innovations have revolutionized the use of EM to investigate structures of cells, viruses and proteins in 3D in unprecedented detail. For the first time, scientists studying protein structure with cryo-EM are able to visualize small, dynamic complexes at atomic resolution. But because many researchers lack access to the latest cryo-EM technologies, the National Cancer Institute is investing in a shared resource, the National Cryo-Electron Microscopy Facility. The facility is projected to open for use by extramural researchers in Fall 2016.
In parallel, the Frederick National Laboratory for Cancer Research and the Center for Cancer Research have partnered to develop the Center for Molecular Microscopy (CMM), a program that supports intramural structural biology research, while also developing new techniques for 3D EM. CMM researchers use both cryo-EM and focused ion beam scanning electron microscopy (FIB-SEM), a relatively new technique that can directly image fine details such as organelles and viruses in cells and tissues in 3D.
With these two new resources, the Frederick National Laboratory is poised to contribute to a fast growing scientific field, one that has the potential to revolutionize both basic structural biology research as well as translational fields such as drug discovery.
Single Dose of HPV Vaccine May Protect against Cervical Cancer
A single dose of the cancer-fighting human papillomavirus (HPV) vaccine Cervarix™ appears to induce an immune
response that remains stable in the blood four years after vaccination. This may be enough to protect women from
two strains of HPV and, ultimately, from HVP-induced cervical cancer.
These findings were published in Cancer
Prevention Research and with the work of researchers from the Costa Rica HPV Vaccine Trial and the
Frederick National Laboratory for Cancer Research. The Costa Rica HPV Vaccine Trial is a long-standing collaboration
between investigators in Costa Rica and National Cancer Institute.
If these findings are confirmed in larger studies and for a longer follow-up time, it could mean fewer return
trips to the doctor’s office for booster shots, and lower overall costs. This could be especially significant
in developing countries where cervical cancer is one of the most common causes of cancer death in women and the
success of vaccination programs are more sensitive to cost and logistical issues.
New treatment for childhood cancer
The Food and Drug Administration has approved dinutuximab (ch14.18) as an immunotherapy for neuroblastoma, a rare cancer that affects children, mostly under age 5. The Frederick National Lab’s Biopharmaceutical Development Program produced ch14.18 for the NCI-sponsored clinical trials that proved the drug’s effectiveness against the disease, which arises in infants and young children as a tumor of immature cells of the peripheral nervous system. More than 650 cases are diagnosed each year in North America. Half of all patients have a high-risk form of the disease and a poor prognosis. Dinutuximab is designed to benefit these high-risk patients. BDP supported transfer of the technology, under an NCI Cooperative Research and Development Agreement, to United Therapeutics Corporation of Silver Spring, Md., and Research Triangle Park, N.C., for commercial production.
Collaboration yields commercial products.
Early in the AIDS epidemic it became evident that blood transfusion was a major
route of exposure with greater than 5000 people/year becoming infected with the
AIDS virus from blood transfusions. In 1984, soon after HIV-1 was discovered and
adapted to growth in cell culture, virus infected cells were transferred to contractor
scientists in what was later to become the AIDS Vaccine Program (AVP) at Frederick
National Lab, for the large scale production of viruses to be used in the development
of diagnostic blood tests. By the end of the first year, 131 lots of purified HIV-1
derived from >12,400 liters of cell culture were prepared. Accomplishing this task
was facilitated by critical unique technical infrastructure capabilities and expertise
at the Frederick National Lab (originally developed for the large scale propagation
and production of retroviruses for cancer related studies) and the flexibility and
rapid response capabilities afforded by the FFRDC organization. The Frederick National
Lab scientists provided large quantities of virus, virus-infected cells and technology
to the private companies that had received licenses to prepare HIV-1 assays. As
a result of this close interaction between the FFRDC contractor staff and the private
companies, commercial diagnostic assays were approved by the FDA within 11 months
of receipt of the virus infected cells at Frederick National Lab. Use of these assays
to detect and discard blood from infected individuals resulted in rapid decrease
of blood transfusion associated infections to less than 500/year.
Harnessing the Power of Nanotechnology to Fight Cancer
The Nanotechnology Characterization Laboratory (NCL) is branching out into two new directions: 1) The introduction of nanotechnology early in the commercial drug development pipeline and 2) The launching of a pan-European infrastructure for nanotechnology characterization.
NCL has begun working with pharmaceutical companies on nanoparticle drug formulations early in the development pipeline with the goal of making cancer medicines more potent with fewer side effects. NCL recently signed collaboration agreements with Amgen, AstraZeneca, and Pfizer. Nanomedicine drug delivery systems have previously been developed for hard-to-treat solid tumors (e.g. breast, lung, pancreas). More recently, nanotech formulations are being targeted to blood cancers and metastases.
Overseas, NCL is joining with eight other partners from France, Germany, Ireland, Italy, Norway, Switzerland, and the United Kingdom to make therapeutic nanotechnologies more widely available internationally. The European Union Nanomedicine Characterisation Laboratory, funded by the European Commission, will be the first translational infrastructure in nanomedicine in the EU.