In lab tests, the researchers showed that these switches, working from inside the cells, can activate a powerful cell-killing drug when the device detects a marker linked to cancer. The goal, the scientists said, is to deploy a new type of weapon that causes cancer cells to self-destruct while sparing healthy tissue.
This new cancer-fighting strategy and promising early lab test results were reported this week in the online early edition of Proceedings of the National Academy of Sciences. Although the switches have not yet been tested on human patients, and much more testing must be done, the researchers say they have taken a positive first step toward adding a novel weapon to the difficult task of treating cancer.
One key problem in fighting cancer is that broadly applied chemotherapy usually also harms healthy cells. In the protein switch strategy, however, a doctor would instead administer a “prodrug,” meaning an inactive form of a cancer-fighting drug. Only when a cancer marker is present would the cellular switch turn this harmless prodrug into a potent form of chemotherapy.
“The switch in effect turns the cancer cell into a factory for producing the anti-cancer drug inside the cancer cell,” said Marc Ostermeier, a Johns Hopkins chemical and biomolecular engineering professor in the Whiting School of Engineering, who supervised development of the switch.
“The healthy cells will also receive the prodrug,” he added, “and ideally it will remain in its non-toxic form. Our hope is that this strategy will kill more cancer cells while decreasing the unfortunate side effects on healthy cells.”
To demonstrate that these switches can work, the research team successfully tested them on human colon cancer and breast cancer cells in Ostermeier’s lab and in the laboratory of James R. Eshleman, a professor of pathology and oncology in the Johns Hopkins School of Medicine.
“This is a radically different tool to attack cancers,” said Eshleman, a co-author of the PNAS journal article, “but many experiments need to be done before we will be able to use it in patients.”
The next step is animal testing, expected to begin within a year, Ostermeier said.
Ostermeier’s team made the cancer-fighting switch by fusing together two different proteins. One protein detects a marker that cancer cells produce. The other protein, from yeast, can turn an inactive prodrug into a cancer-cell killer. “When the first part of the switch detects cancer, it tells its partner to activate the chemotherapy drug, destroying the cell,” Ostermeier said.
In order for this switch to work, it must first get inside the cancer cells. Ostermeier said this can be done through a technique in which the switch gene is delivered inside the cell. The switch gene serves as the blueprint from which the cell’s own machinery constructs the protein switch. Another approach, he said, would be to develop methods to deliver the switch protein itself to cells.
Once the switches are in place, the patient would receive the inactive chemotherapy drug, which would turn into a cancer attacker inside the cells where the switch has been flipped on.
Although many researchers are developing methods to deliver anti-cancer drugs specifically to cancer cells, Ostermeier said the protein switch tactic skirts difficulties encountered in those methods.
“The protein switch concept changes the game by providing a mechanism to target production of the anti-cancer drugs inside cancer cells instead of targeting delivery of the anti-cancer drug to cancer cells,” he said.
The lead author of the PNAS study was Chapman M. Wright, who worked on the project as an assistant research scientist in Ostermeier’s lab and who now works for a private biotech company. Co-authors on the paper were Ostermeier, Eshleman and R. Clay Wright (not related to Chapman Wright), a doctoral student in Ostermeier’s lab. Through the Johns Hopkins Technology Transfer office, Ostermeier and Chapman Wright have filed for patent protection covering the protein switch for cancer technology.The research was funded by the National Institutes of Health. The paper, “A protein therapeutic modality founded on molecular recognition,” can be viewed online at:
Phil Sneiderman | Newswise Science News
Glycosylation: Mapping Uncharted Territory
21.09.2017 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
Molecular Force Sensors
20.09.2017 | Max-Planck-Institut für Biochemie
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
21.09.2017 | Life Sciences
21.09.2017 | Health and Medicine
21.09.2017 | Earth Sciences