Personalized Skin Cancer Vaccine

Two major pharmaceutical companies are testing a personalized vaccine that might prevent the recurrence of a specific type of skin cancer. Moderna, one of the companies behind the COVID-19 vaccine, and Merck, an enterprise focused largely on oncology and preventative medicines, are teaming up to see if they can reduce the public’s risk of re-developing the deadliest form of skin cancer: melanoma.

The vaccine essentially combines two medical technologies: the mRNA vaccine and Merck’s Keytruda. As with the COVID-19 vaccine, mRNA shots don’t require an actual virus. Instead, they use a disease’s genetic code to “teach” the immune system to recognize and fight that particular illness. This makes it relatively easy and inexpensive for scientists to develop mRNA vaccines and edit them if a new form of the disease emerges. Keytruda, meanwhile, is a prescription medication that helps prevent melanoma from coming back after known cancer cells have been surgically removed.

Moderna and Merck are testing the feasibility of not only creating a two-in-one drug with both technologies but also customizing individual vaccines to suit their respective patients. Each vaccine is engineered to activate the patient’s immune system, which in turn deploys T cells (a type of white blood cell known to fight cancer) that go after the specific mutations of a patient’s tumor. Keytruda assists this effort by barring certain cell proteins from getting in the way of T cells’ intervention.

The experimental drug is currently in its second clinical trial out of three. The trial involves 157 participants with high-risk melanoma who just successfully underwent surgical removal. Some of the participants were given the personalized vaccine, while others were given Keytruda alone. Moderna and Merck will observe whether the participants’ melanoma returns over the span of approximately one year, with primary data expected at the end of this year.

If a vaccine preventing the recurrence of melanoma does in fact become commercially available, it could prevent more than 7,000 deaths per year in the US alone.

Source: https://www.extremetech.com/

Light-activated Immunotherapy Kills Brain Cancer

Scientists at the Institute of Cancer Research in London have developed a new light-activated photoimmunotherapy” that could help treat brain cancer. The key is a compound that glows under light to guide surgeons to the tumor, while near-infrared light activates a cancer-killing mechanism.

The new study builds on a common technique called Fluorescence Guided Surgery (FGS), which involves introducing a fluorescent agent to the body which glows under exposure to light. This is paired with a synthetic molecule that binds to a specific protein, such as those expressed by cancer cells. The end result is tumors that glow under certain lighting conditions or imaging, guiding surgeons to remove the affected cells more precisely.

For the new study, the researchers gave the technique an extra abilitykilling the cancer as well. They added a new molecule that binds to a protein called EGFR, which is often mutated in cases of the brain cancer glioblastoma. After the fluorescence has helped surgeons remove the bulk of the tumor, they can shine near-infrared light on the site, which switches the compound into a tumor-killing mode by releasing reactive oxygen species. The idea is to kill off any remaining cells that could – and often do – stage an aggressive comeback after surgery.

In tests in mice with glioblastoma, the researchers showed that animals treated with the new technique had clear signs of tumor cell death in as little as one hour after exposure to near-infrared light. On top of that, the treatment also caused the animals’ immune systems to mount a new attack on the cancer, which could help reduce the chances of relapse.

Our study shows that a novel photoimmunotherapy treatment using a combination of a fluorescent marker, ‘affibody’ protein and near-infrared light can both identify and treat leftover glioblastoma cells in mice,” said Dr. Gabriela Kramer-Marek, lead author of the study. “In the future, we hope this approach can be used to treat human glioblastoma and potentially other cancers too.”

The team says the technique could also eventually be used to treat other types of cancer. The research was published in the journal BMC Medicine.

Source: https://www.icr.ac.uk/
AND
https://newatlas.com/

‘Masked’ Cancer Drug Sneaks Through Body

Many cancer treatments are notoriously savage on the body; they attack healthy cells at the same time as tumor cells, causing a plethora of side effects. Now, researchers at the University of Chicago’s Pritzker School of Molecular Engineering (PME) have designed a method to keep one promising cancer drug from wreaking such havoc. The team has engineered a new “masked” version of the immunotherapy drug interleukin-12 that is activated only when it reaches a tumor.

Researchers have long suspected that interleukin-12 could be a powerful cancer treatment, but it caused dangerous side effects. Now, Pritzker Molecular Engineering researchers have developed a version of the molecule not activated until it reaches a tumor, where it eradicates cancer cells.

Our research shows that this masked version of IL-12 is much safer for the body, but it possesses the same anti-tumor efficacy as the original,” said Aslan Mansurov, a postdoctoral research fellow and first author of the new paper. He carried out the IL-12 engineering work with Jeffrey Hubbell, the Eugene Bell Professor in Tissue Engineering, who co-leads PME’s Immunoengineering research theme with professor Melody Swartz.

Researchers know that IL-12 potently activates lymphocytes, immune cells with the potential to destroy tumor cells. But, in the 1990s, early clinical trials of IL-12 were halted because of severe, toxic side effects in patients. The same immune activation that started a cascade of events killing cancer cells also led to severe inflammation throughout the body. IL-12, at least in its natural form, was shelved.
The research on the molecule, also known as IL-12, is described in the journal Nature Biomedical Engineering.

But Mansurov, Hubbell, Swartz, and colleagues had an idea to reinvigorate the possibility of IL-12. What if the drug could slip through the body without activating the immune system? They designed a “masked molecule with a cap covering the section of IL-12 which normally binds immune cells. The cap can be removed only by tumor-associated proteases, a set of molecular scissors found in the vicinity of tumors to help them degrade surrounding healthy tissue. When the proteases chop off the cap, the IL-12 becomes active, able to spur an immune response against the tumor.

The masked IL-12 is largely inactive everywhere in the body except at the site of the tumor, where these proteases can cleave off the mask,” explained Mansurov.

Source: https://pme.uchicago.edu/

Lasers and Ultrasound Combine to Pulverize Arterial Plaque

Lasers are one of the tools physicians can lean on to tackle plaque buildup on arterial walls, but current approaches carry a risk of complications and can be limited in their effectiveness. By bringing ultrasound into the mix, scientists at the University of Kansas have demonstrated a new take on this treatment that relies on exploding microbubbles to destroy plaque with greater safety and efficiency, while hinting at some unique long-term advantages.

Scientists have demonstrated a new technique to take out arterial plaque, using low-power lasers and ultrasound to break it apart with tiny bubbles

The novel ultrasound-assisted laser technique builds off what’s known as laser angioplasty, an existing treatment designed to improve blood flow in patients suffering from plaque buildup that narrows the arteries. Where more conventional treatments such as stents and balloon angioplasty expand the artery and compress the plaque, laser angioplasty destroys it to eliminate the blockage.

The laser is inserted into the artery with a catheter, and the thermal energy it generates turns water in the artery into a vapor bubble that expands, collapses and breaks up the plaque. Because this technique calls for high-power lasers, it has the potential to perforate or dissect the artery, something the scientists are looking to avoid by using low-power lasers instead.

They were able to do so in pork belly samples and ex vivo samples of artery plaque with the help of ultrasound. The method uses a low-power nanosecond pulsed laser to generate microbubbles, and applying ultrasound to the artery then causes these microbubbles to expand, collapse and disrupt the plaque.

In conventional laser angioplasty, a high laser power is required for the entire cavitation process, whereas in our technology, a lower laser power is only required for initiating the cavitation process,” said team member Rohit Singh. “Overall, the combination of ultrasound and laser reduces the need for laser power and improves the efficiency of atherosclerotic plaque removal.

The mix of lasers and ultrasound has shown potential in other areas of medicine, with Singh and his colleagues pursuing similar therapies to tackle abnormal microvessels in the eye that cause blindness and blood clots in the veins. We’ve also seen ultrasound used to explode tiny bubbles in cancer research, providing a way of wiping out cancerous cells within a tumor.

Source: https://newatlas.com/

Natural Killer Cells, Primed with an Antibody, Induce Remissions in Patients with Advanced Lymphoma

Two patients with advanced Hodgkin lymphoma were told their tumors were
so resistant to treatment that hospice was their best option. Then, they were
enrolled in a clinical trial of a novel immunotherapy involving so-called
natural killer cells. After treatment, they saw complete remission.
Researchers say the results are a hopeful if preliminary sign of the potential of immunotherapies harnessing natural killer, or NK, cellsinnate immune system cells that have certain advantages over the more commonly recognized adaptive T cell cancer therapies.
The treatment in the study, developed by the University of Texas MD Anderson Cancer Center and the German drug maker Affimed, combined offthe-shelf NK cells with a separate antibody that primes the cells to recognize a specific protein signature of the tumors. Two additional patients administered
the same treatment have shown ongoing partial responses.

These results show you just how powerful NK cells are,” said Katy Rezvani,
a stem-cell transplant physician and NK cell researcher at MD Anderson, who
is spearheading the development of this new treatment.
It’s amazing when you see these responses for patients who have so few
options, patients who’ve been told that they should go to hospice,” Rezvani
said.“I cannot begin to tell you how satisfying this is for clinicians.
Data from the study is to be presented at the annual meeting of the American
Association for Cancer Research (AACR).
Source: https://www.mdanderson.org/
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https://www.mskcc.org/

Ultrasound to Command Bacteria to Nuke Tumors

Scientists at Caltech have genetically engineered, sound-controlled bacteria that seek and destroy cancer cells. In a new paper appearing in the journal Nature Communications, researchers from the lab of Mikhail Shapiro, professor of chemical engineering and Howard Hughes Medical Institute investigator, show how they have developed a specialized strain of the bacteria Escherichia coli (E. coli) that seeks out and infiltrates cancerous tumors when injected into a patient’s body. Once the bacteria have arrived at their destination, they can be triggered to produce anti-cancer drugs with pulses of ultrasound.

The goal of this technology is to take advantage of the ability of engineered probiotics to infiltrate tumors, while using ultrasound to activate them to release potent drugs inside the tumor,” Shapiro says.

The starting point for their work was a strain of E. coli called Nissle 1917, which is approved for medical uses in humans. After being injected into the bloodstream, these bacteria spread throughout the body. The patient’s immune system then destroys them—except for those bacteria that have colonized cancerous tumors, which offer an immunosuppressed environment.

To turn the bacteria into a useful tool for treating cancer, the team engineered them to contain two new sets of genes. One set of genes is for producing nanobodies, which are therapeutic proteins that turn off the signals a tumor uses to prevent an anti-tumor response by the immune system. The presence of these nanobodies allow the immune system to attack the tumor. The other set of genes act like a thermal switch for turning the nanobody genes on when the bacteria reaches a specific temperature.

By inserting the temperature-dependent and nanobody genes, the team was able to create strains of bacteria that only produced the tumor-suppressing nanobodies when warmed to a trigger temperature of 42–43 degrees Celsius. Since normal human body temperature is 37 degrees Celsius, these strains do not begin producing their anti-tumor nanobodies when injected into a person. Instead, they quietly grow inside the tumors until an outside source heats them to their trigger temperature.

But how do you heat bacteria that are located in one specific location, potentially deep inside the body where a tumor is growing? For this, the team used focused ultrasound (FUS). FUS is similar to the ultrasound used for imaging internal organs, or a fetus growing in the womb, but has higher intensity and is focused into a tight point. Focusing the ultrasound on one spot causes the tissue in that location to heat up, but not the tissue surrounding it; by controlling the intensity of the ultrasound, the researchers were able to raise the temperature of that tissue to a specific degree.

Source: https://www.caltech.edu/

Microrobot Fish Swims Through the Body to Vomit Drugs on cancer

Delivering chemotherapy drugs directly to cancers could help reduce side effects, and soon that job could be done by tiny 3D-printed robotic animals. These microrobots are steered by magnets, and only release their drug payload when they encounter the acidic environment around a tumor.

A new microrobot fish could one day swim through the body with a mouthful of drugs, and automatically spit them up when it encounters cancer cells

The new microrobots are made of hydrogel 3D printed into the shape of different animals, like a fish, a crab and a butterfly, with voids that can carry particles. The team adjusted the printing density in specific areas, like the edges of the crab’s claws or the fish’s mouth, so that they can open or close in response to changes in acidity. Finally, the microrobots were placed in a solution containing iron oxide nanoparticles to make them magnetic.

The end result was microrobots that could be loaded up with drug nanoparticles and steered towards a target location using magnets, where they would release their payload automatically due to changes in pH levels.

In lab tests, the researchers used magnets to guide a fish microrobot through simulated blood vessels, towards a cluster of cancer cells at one end. In that area, the team made the solution slightly more acidic and the fish opened its mouth and spat out the drugs on cue, killing the cancer cells. In other tests, crab microrobots could be made to clasp drug nanoparticles with their claws, scuttle to a target location, and release them.

Source: https://newatlas.com/

Synthetic Molecule Seeks out and Destroys Cancer Tumors

Activating the immune system at the site of a tumor can recruit and stimulate immune cells to destroy tumor cells. One strategy involves injecting immune-stimulating molecules directly into the tumor, but this method can be challenging for cancers that are not easily accessible.  Now, Stanford researchers have developed a new synthetic molecule that combines a tumor-targeting agent with another molecule that triggers immune activation. This tumor-targeted immunotherapy can be administered intravenously and makes its way to one or multiple tumor sites in the body, where it recruits immune cells to fight the cancer

Three doses of this new immunotherapy prolonged the survival of six of nine laboratory mice with an aggressive triple negative breast cancer. Of the six, three appeared cured of their cancer over the duration of the monthslong study. A single dose of this molecule induced complete tumor regression in five of 10 mice. The synthetic molecule showed similar results in a mouse model of pancreatic cancer.

We essentially cured some animals with just a few injections,” said Jennifer Cochran, PhD, the Shriram Chair of the Department of Bioengineering. “It was pretty astonishing. When we looked within the tumors, we saw they went from a highly immunosuppressive microenvironment to one full of activated B and T cells — similar to what happens when the immune-stimulating molecule is injected directly into the tumor. So, we’re achieving intra-tumoral injection results but with an IV delivery.”

A paper describing the study has been published online in Cell Chemical Biology. Cochran shares senior authorship with Carolyn Bertozzi, PhD, the Baker Family Director of Stanford ChEM-H, Anne T. and Robert M. Bass Professor in the School of Humanities and Sciences and professor of chemistry; and Ronald Levy, MD, the Robert K. and Helen K. Summy Professor in the School of Medicine. The lead authors are graduate student Caitlyn Miller and instructor of medicine Idit Sagiv-Barfi, PhD.

Source: https://med.stanford.edu/
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https://www.thebrighterside.news/

How to Make Tumor Eliminate Itself

A new technology developed by University of Zurich (UZH) researchers in Switzerland enables the body to produce therapeutic agents on demand at the exact location where they are needed. The innovation could reduce the side effects of cancer therapy and may hold the solution to better delivery of Covid-related therapies directly to the lungs.

Scientists have modified a common respiratory virus, called adenovirus, to act like a Trojan horse to deliver genes for cancer therapeutics directly into tumor cells. Unlike chemotherapy or radiotherapy, this approach does no harm to normal healthy cells. Once inside tumor cells, the delivered genes serve as a blueprint for therapeutic antibodies, cytokines and other signaling substances, which are produced by the cancer cells themselves and act to eliminate tumors from the inside out.

Imaris Snapshot

View of the tumor from the inside. A piece of the tumor was made completely transparent and scanned in 3D with a special microscope. The components labeled with fluorescent colors were rendered in a rotatable 3D representation on the computer (red: blood vessels, turquoise: tumor cells, yellow: therapeutic antibody)

We trick the tumor into eliminating itself through the production of anti-cancer agents by its own cells,” says postdoctoral fellow Sheena Smith, who led the development of the delivery approach. Research group leader Andreas Plückthun explains: “The therapeutic agents, such as therapeutic antibodies or signaling substances, mostly stay at the place in the body where they’re needed instead of spreading throughout the bloodstream where they can damage healthy organs and tissues.”

The UZH researchers call their technology SHREAD: for SHielded, REtargetted ADenovirus. It builds on key technologies previously engineered by the Plückthun team, including to direct adenoviruses to specified parts of the body to hide them from the immune  system. With the SHREAD system, the scientists made the tumor itself produce a clinically approved breast cancer antibody, called trastuzumab (Herceptin®), in the mammary of a mouse. They found that, after a few days, SHREAD produced more of the antibody in the tumor than when the drug was injected directly. Moreover, the concentration in the bloodstream and in other tissues where side effects could occur were significantly lower with SHREAD. The scientists used a very sophisticated, high-resolution 3D imaging method and tissues rendered totally transparent to show how the therapeutic antibody, produced in the body, creates pores in blood vessels of the tumor and destroys tumor cells, and thus treats it from the inside.

Source: https://www.media.uzh.ch/

Nano BiosuperCapacitor Provides Energy for Biomedical Applications

The miniaturization of microelectronic sensor technology, microelectronic robots or intravascular implants is progressing rapidly. However, it also poses major challenges for research. One of the biggest is the development of tiny but efficient energy storage devices that enable the operation of autonomously working microsystems – in more and more smaller areas of the human body for example. In addition, these energy storage devices must be bio-compatible if they are to be used in the body at all. Now there is a prototype that combines these essential properties. The breakthrough was achieved by an international research team led by Prof. Dr. Oliver G. Schmidt, Professorship of Materials Systems for Nanoelectronics at Chemnitz University of Technology (Germany), initiator of the Center for Materials, Architectures and Integration of Nanomembranes (MAIN) at Chemnitz University of Technology and director at the Leibniz Institute for Solid State and Materials Research (IFW) Dresden. The Leibniz Institute of Polymer Research Dresden (IPF) was also involved in the study as a cooperation partner.

In the current issue of Nature Communications, the researchers report on the smallest microsupercapacitors to date, which already functions in (artificial) blood vessels and can be used as an energy source for a tiny sensor system to measure pH.

This storage system opens up possibilities for intravascular implants and microrobotic systems for next-generation biomedicine that could operate in hard-to-reach small spaces deep inside the human body. For example, real-time detection of blood pH can help predict early tumor growing. “It is extremely encouraging to see how new, extremely flexible, and adaptive microelectronics is making it into the miniaturized world of biological systems“, says research group leader Prof. Dr. Oliver G. Schmidt, who is extremely pleased with this research success.

The architecture of our nano-bio supercapacitors offers the first potential solution to one of the biggest challenges – tiny integrated energy storage devices that enable the self-sufficient operation of multifunctional microsystems,” says Dr. Vineeth Kumar, researcher in Prof. Schmidt’s team and a research associate at the MAIN research center.

Ever smaller energy storage devices in the submillimeter range – so-called “nano-supercapacitors” (nBSC) – for even smaller microelectronic components are not only a major technical challenge, however. This is because, as a rule, these supercapacitors do not use biocompatible materials but, for example, corrosive electrolytes and quickly discharge themselves in the event of defects and contamination. Both aspects make them unsuitable for biomedical applications in the body. So-called “biosupercapacitors (BSCs)” offer a solution. They have two outstanding properties: they are fully biocompatible, which means that they can be used in body fluids such as blood and can be used for further medical studies.

In addition, biosupercapacitors can compensate for self-discharge behavior through bio-electrochemical reactions. In doing so, they even benefit from the body’s own reactions. This is because, in addition to typical charge storage reactions of a supercapacitor, redox enzymatic reactions and living cells naturally present in the blood increase the performance of the device by 40%.

Source: https://www.tu-chemnitz.de/