How mRNA Vaccine Eradicates Pancreatic Cancer

Calendar February 22, 2023 | Posted by admin

Messenger RNA (mRNA) vaccines may be the hottest thing in science now, as they helped turn the tide against COVID-19. But even before the pandemic began, Memorial Sloan Kettering Cancer Center researchers had already been working to use mRNA vaccine technology to treat cancer. Vinod Balachandran a physician-scientist affiliated with the David M. Rubenstein Center for Pancreatic Cancer Research and the Parker Institute for Cancer Immunotherapy, is leading the only clinical trial to test mRNA vaccines for pancreatic cancer. The key to these vaccines appears to be proteins in the pancreatic tumors, called neoantigens, which alert the immune system to keep the cancer at bay.

The vaccines are custom-made for every person. The hope is that the vaccine will stimulate the production of certain immune cells, called T cells, that recognize pancreatic cancer cells. This could reduce the risk of the cancer returning after the main tumor was removed by surgery. In 8 of 16 patients studied, the vaccines activated T cells that recognize the patient’s own pancreatic cancers. These patients also showed delayed recurrence of their pancreatic cancers, suggesting the T cells activated by the vaccines may be having the desired effect to keep pancreatic cancers in check. 

There has been great interest in using immunotherapy for pancreatic cancer because nothing else has worked very well. We thought immunotherapy held promise because of research we began about seven years ago. A small subset of patients with pancreatic cancer manage to beat the odds and survive after their tumor is removed. We looked at the tumors taken from these select patients and saw that the tumors had an especially large number of immune cells in them, especially T cells. Something in the tumor cells seemed to be sending out a signal that alerted the T cells and drew them in.

Source: https://www.thebrighterside.news/

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How to Kill Cancer Before Birth

Calendar February 6, 2023 | Posted by admin

Genes that trigger cancer could be turned off - before people are even born, according to new research. Scientists have found a tumour 'switch' that develops hours after fertilisation. The discovery offers hope of a screening program, personalised vaccines - or even embryo engineering.

"Our work could open a new clinical chapter for the early detection of cancer," sait Co author Professor Tony Perry, of the University of Bath.

In experiments on mice, the international team found gene activity in embryos kicks off within four hours of sperm injection. These include 'oncogenes' which have the potential to cause cancer - if mutated. The findings are expected to apply to humans. "Many factors responsible for the dawn of gene activity in embryos have long been known to be major oncogenes," explained Prof Perry. It is the first time a pre-set order of events has been established in one-cell embryos in any species.

When an embryo is formed, its genes – donated by a fertilising sperm and egg – are silent. Somehow, at an early stage of development, embryo genes must be switched on. Without this vital 'genes on' switch in the embryo, none of us would be here, yet surprisingly little is known about what the switch looks like, or the identity of the 'molecular finger' that pushes the switch.

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RNA Technology to Erase Age-related Wrinkles

Calendar January 23, 2023 | Posted by admin

A team of researchers led by The University of Texas MD Anderson Cancer Center has developed a novel delivery system for messenger RNA (mRNA) using extracellular vesicles (EVs). The new technique has the potential to overcome many of the delivery hurdles faced by other promising mRNA therapies.
In the study, published today in Nature Biomedical Engineering, the researchers use EV-encapsulated mRNA to initiate and sustain collagen production for several months in the cells of photoaged skin in laboratory models. It is the first therapy to demonstrate this ability and represents a proof-of-concept for deploying the EV mRNA therapy.

“This is an entirely new modality for delivering mRNA,” said corresponding author Betty Kim, M.D., Ph.D., professor of Neurosurgery. “We used it in our study to initiate collagen production in cells, but it has the potential to be a delivery system for a number of mRNA therapies that currently have no good method for being delivered.”
The genetic code for building specific proteins is contained in mRNA but delivering mRNA within the body is one of the largest hurdles facing clinical applications of many mRNA-based therapies. The current COVID-19 vaccines, which marked the first widespread use of mRNA therapy, use lipid nanoparticles for delivery, and the other primary delivery systems for genetic materials so far have been viral based. However, each of these approaches comes with certain limitations and challenges.

Extracellular vesicles are small structures created by cells that transport biomolecules and nucleic acids in the body. These naturally occurring particles can be modified to carry mRNAs, which gives them the benefit of innate biocompatibility without triggering a strong immune response, allowing them to be administered multiple times. Additionally, their size allows them to carry even the largest human genes and proteins.

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Sanofi Covid Vaccine Shows 100% Efficacy Against Severe Disease

Calendar February 24, 2022 | Posted by admin

Sanofi and GlaxoSmithKline Plc, the pharma giants that stumbled in the race to develop a Covid-19 shot, found their vaccine protects against severe disease and hospitalization and will submit data to regulators for clearance. The duo said data from a trial shows that two doses of the Sanofi-GSK vaccine have 100% efficacy against severe Covid-19 and hospitalizations and 58% efficacy against any symptomatic Covid-19 disease. They said the safety of the vaccine was favorable too.

Meanwhile, a separate study showed it could increase neutralizing antibody levels 18- to 30-fold when used as a booster in people who’ve received other types of shots first. Shares in Sanofi rose as much as 1.7% in Paris on Wednesday, while GSK rose as much as 1.6% in London.

The data should allow the vaccine giants to finally play a big role in the pandemic fight, after repeated development delays allowed nimbler competitors like Moderna Inc. and the BioNTech SE–Pfizer Inc. alliance to rush ahead with messenger-RNA products. Those companies, along with AstraZeneca Plc and Johnson & Johnson, steered highly effective products rapidly to market, helping save millions of lives and earning tens of billions of dollars in revenue.

While the Sanofi-Glaxo product appears to be on par with the mRNA shots when it comes to preventing severe disease and hospitalization, the efficacy may trail somewhat in terms of symptomatic disease, Sam Fazeli, an analyst at Bloomberg Intelligence, said in a note.

“The vaccine will find a place among people reticent to take mRNA vaccines and in lower-income countries, making for a modest commercial impact on Sanofi and Glaxo,” Fazeli said.

Source: https://www.bloomberg.com/

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Moderna Starts Human Trials for its Revolutionary HIV Vaccine Today

Calendar August 19, 2021 | Posted by admin

Today, the biotech company Moderna will start human trials for its HIV vaccine. Its HIV vaccine will be the first of its kind to use messenger RNA (mRNA), an approach that Moderna used in its effective COVID-19 vaccine.

The clinical trials will end sometime around spring 2023, according to the National Institutes of Health’s trial registry. They will involve 56 HIV-negative participants aged 18 to 56. The participants will be given one or two forms of mRNA that cause the body to form defenses against HIV infection.

In the past, HIV vaccines used inactivated forms of the virus. However, previous trials showed that these forms didn’t produce any immune responses. In fact, researchers canceled one trial in Thailand during the 2000s after inactivated forms of the virus were found to actually increase people’s risk of catching HIV rather than preventing infections.

Instead, the Moderna trials will contain one of two different types of mRNA: mRNA-1644 and mRNA-1644v2. These get the body’s cells to develop a “protein spike” on their surfaces. These spikes are similar to those embedded by HIV on a cell’s surface when it begins to infect cells to reproduce. When the body recognizes the presence of the mRNA spike, it begins producing antibodies to protect against infection. The mRNA may also allow scientists to make tweaks to the vaccine more easily.

“The mRNA platform makes it easy to develop vaccines against variants because it just requires an update to the coding sequences in the mRNA that code for the variant,” Rajesh Gandhi, MD, an infectious diseases physician at Massachusetts General Hospital and chair of the HIV Medicine Association, told the medical site Verywell. This is especially helpful for HIV since the virus is known for having mutated into at least 16 known variants.

Source: https://www.lgbtqnation.com/

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How Does an mRNA Vaccine Work?

Calendar January 20, 2021 | Posted by admin

The COVID-19 pandemic has brought unusual attention to everything from handwashing to polymerase chain reaction (PCR) tests. As we move into the later stages of this pandemic, though, a different scientific concept has dominated the national conversation: vaccines. The study of the human immune system and how vaccines influence it is complex and sometimes counterintuitive, and the deployment of a new method for immunization based on mRNA has made it all the more confusing.

The two vaccines that have received Emergency Use Authorizations (EUAs) from the Food and Drug Administration are both mRNA vaccines. And since they’re our only hope for ending this pandemic, it’s crucial to understand how they work—and why you should get one.

Vaccines come in a few main forms, but they share the same central goal: equip our immune systems with the tools to handily defeat a pathogen we might encounter in the future. Think of it like a practice round before your body sees the real thing.

The exact way our bodies develop this preemptive immunity depends on the kind of vaccine we’re given. Live-attenuated vaccines provide our cells with a weakened version of a pathogen; protein subunit vaccines give just one part of a bad guy, so immune cells know how to recognize that part of a virus or bacterium. But mRNA (short for messenger RNA) vaccines actually provide our cells with the instructions for making a protein from the pathogen, in essence creating their own practice dummy. Our own cells produce the viral protein specific to, say, SARS-CoV-2, and then our immune system learns to recognize the proteins.

Source: https://www.popsci.com/

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Immune System Killer Cells Controlled By Circadian Rhythms

Calendar January 14, 2021 | Posted by admin

An analysis of an exhaustive dataset on cells essential to the mammalian immune system shows that our ability to fight disease may rely more heavily on daily circadian cycles than previously assumed.

Malfunctions in , the process that keeps our bodies in tune with the day/night cycles, are increasingly associated with diabetes, cancer, Alzheimer’s, and many other diseases. An investigation published today in Genome Research shows that the activity of macrophages—cells within us that seek and destroy intruders like bacteria—may time daily changes in their responses to pathogens and stress through the circadian control of metabolism. In this study, Jennifer Hurley, the Richard Baruch M.D. Career Development Assistant Professor of Biological Sciences at Rensselaer Polytechnic Institute and senior author on this study, and her team investigated how the levels of RNA and proteins in macrophages change over two days.

“We have shown there is an incredible amount of circadian timing of macrophage behavior, but the clock is timing macrophages in unexpected ways” said Hurley.

The circadian system is comprised of a set of core clock proteins that anticipate the day/night cycle by causing daily oscillations in levels of enzymes and hormones, and ultimately affecting physiological parameters such as body temperature and the immune response. This molecular clock marks time through a self-regulating cycle of  production and decay. The “positive” element proteins of the clock trigger production of the “negative” element proteins, which in turn block production of positive element proteins until the negative element proteins decay, thus creating a negative feedback cycle that occurs once every 24 hours.

Positive element proteins also regulate fluctuations in a substantial number of gene products, known as messenger RNA or mRNA. Genetic instructions are transcribed from DNA to mRNA, which are then used as a recipe for assembling proteins, the functional building blocks of the cell. It has long been assumed that the levels of each subsequent step could be predicted from the previous. If that were the case, oscillating mRNA would correspond with oscillating levels of cellular proteins, and therefore, if one could track mRNA, they would know what proteins the circadian clock controlled in the cell.

However, this investigation showed that this paradigm may not always be true. The analysis of the macrophage dataset revealed that there was a substantial mismatch between the proteins and mRNAs that are controlled by the circadian clock. This data paralleled research published in Cell Systems in 2018 by the Hurley lab, showing that about 40% of oscillating proteins in the fungus and circadian model system, Neurospora crassa, had no corresponding oscillating mRNA.

“But the scale of the difference in macrophages really surprised us,” Hurley said. “Eighty percent of the proteins that oscillate don’t have associated oscillating mRNA in macrophages. That means we were really missing how the clock was timing immunity.”

Source: https://medicalxpress.com/

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CRISPR Treatment Destroys Cancer Cells

Calendar November 23, 2020 | Posted by admin

Researchers at Tel Aviv University (TAU) have demonstrated that the CRISPR/Cas9 system is very effective in treating metastatic cancers, a significant step on the way to finding a cure for cancer. The researchers developed a novel lipid nanoparticle-based delivery system that specifically targets cancer cells and destroys them by genetic manipulation. The system, called CRISPR-LNPs, carries a genetic messenger (messenger RNA), which encodes for the CRISPR enzyme Cas9 that acts as molecular scissors that cut the cells’ DNA.

The revolutionary work was conducted in the laboratory of Prof. Dan Peer at TAU. Dr. Daniel Rosenblum led the research together with Ph.D. student Anna Gutkin and colleagues.

To examine the feasibility of using the technology to treat cancer, Prof. Peer and his team chose two of the deadliest cancers: glioblastoma and metastatic ovarian cancer. Glioblastoma is the most aggressive type of brain cancer, with a life expectancy of 15 months after diagnosis and a five-year survival rate of only 3%. The researchers demonstrated that a single treatment with CRISPR-LNPs doubled the average life expectancy of mice with glioblastoma tumors, improving their overall survival rate by about 30%. Ovarian cancer is a major cause of death among women and the most lethal cancer of the female reproductive system. Most patients are diagnosed at an advanced stage of the disease when metastases have already spread throughout the body. Despite progress in recent years, only a third of the patients survive this disease. Treatment with CRISPR-LNPs in a metastatic ovarian cancer mice model increased their overall survival rate by 80%.

“The CRISPR genome editing technology, capable of identifying and altering any genetic segment, has revolutionized our ability to disrupt, repair or even replace genes in a personalized manner,” said Prof. Peer. “Despite its extensive use in research, clinical implementation is still in its infancy because an effective delivery system is needed to safely and accurately deliver the CRISPR to its target cells. The delivery system we developed targets the DNA responsible for the cancer cells’ survival. This is an innovative treatment for aggressive cancers that have no effective treatments today.”

“This is the first study in the world to prove that the CRISPR genome editing system can be used to treat cancer effectively in a living animal,” explained Prof. Peer. “It must be emphasized that this is not chemotherapy. There are no side effects, and a cancer cell treated in this way will never become active again. The molecular scissors of Cas9 cut the cancer cell’s DNA, thereby neutralizing it and permanently preventing replication.”

The results of the groundbreaking study were published in November 2020 in Science Advances.

Source: https://english.tau.ac.il/
AND
 https://www.eurekalert.org/

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Pfizer Says Its COVID-19 Vaccine Is 95% Effective

Calendar November 18, 2020 | Posted by admin

Pfizer and BioNTech said Wednesday that a final data analysis found their coronavirus vaccine was 95% effective in preventing COVID-19 and, in addition, appeared to fend off severe disease.

Vaccine, called BNT162b2, was highly effective against the virus 28 days after the first dose, and its effectiveness was consistent across all ages, races and ethnicities, the drugmakers said. Additionally, the elderly, who are seen as at high risk of severe illness from COVID-19, saw vaccine effectiveness of more than 94%, they added.

“The final analysis underlines the results of the positive interim efficacy analysis announced on November 9,” BioNTech CEO Ugur Sahin said in a statement. “The data indicates that our vaccine … is able to induce a high rate of protection against COVID-19 only 29 days after the first dose. In addition, the vaccine was observed to be well-tolerated in all age groups with mostly mild to moderate side effects, which may be due in part to the relatively low dose.”

The vaccine also appeared to prevent severe disease in volunteers. There were 10 cases of severe cases of COVID-19 observed in the phase three trial, with nine of the cases occurring in the placebo group, the companies said. There were also no “serious” safety concerns, they said, with most adverse events resolving shortly after vaccination. The company’s shares jumped 3% in premarket trading.

The final analysis evaluated 170 confirmed COVID-19 infections among the late-stage trial’s more than 43,000 participants. The companies said 162 cases of COVID-19 were observed in the placebo group versus eight cases observed in the group that received its two-dose vaccine. That resulted in an estimated vaccine efficacy of 95%, they said.

The news comes more than a week after the companies announced that their vaccine was more than 90% effective and two days after Moderna said preliminary phase three trial data showed its vaccine was 94.5%. Both vaccines use messenger RNA, or mRNA, technology. It’s a new approach to vaccines that uses genetic material to provoke an immune response.

A safe and effective vaccine is seen by investors and policymakers as a solution to get the global economy back on track after the pandemic wreaked havoc on nearly every country across the globe and upended businesses. The virus continues to spread rapidly, with more than 55.6 million cases worldwide and at least 1.33 million deaths as of Wednesday, according to data compiled by Johns Hopkins University.

Pfizer and BioNTech‘s initial results on Nov. 9 were based on the first interim efficacy analysis conducted by an external and independent Data Monitoring Committee from the phase three clinical trial. The independent group of experts oversees U.S. clinical trials to ensure the safety of participants. Medical experts note it remains unclear how long the vaccines will provide immunity and whether or how often people may need periodic booster shots.

“These vaccines are going to be approved and then rolled out with basically a few months’ worth of data. You’re not going to do a two-year study to see whether it’s effective for two years with more than 200,000 people dying this year” in the U.S., Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia, said in a recent interview.

Pfizer said it plans to submit an application for emergency use authorization to the Food and Drug Administration “within days.” Pfizer CEO Albert Bourla said at Tuesday’s New York Times Dealbook conference that the company had accumulated enough safety data needed to submit the vaccine for review.

The companies reiterated that they expect to produce up to 50 million doses this year and up to 1.3 billion doses in 2021. They also said they are “confident” in their ability to distribute the vaccine, which requires a storage temperature of minus 94 degrees Fahrenheit. By comparison, Moderna‘s vaccine can be stored for up to six months at negative 4 degrees Fahrenheit.

Source: https://www.nbcdfw.com/

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