March 28, 2023
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Dozens of clinical trials are testing mRNA treatment vaccines in people with various types of cancer, including pancreatic cancer, colorectal cancer, and melanoma. Some vaccines are being evaluated in combination with drugs that enhance the body’s immune response to tumors. But no mRNA cancer vaccine has been approved by the US Food and Drug Administration for use either alone or with other cancer treatments.
“mRNA vaccine technology is extremely promising for infectious diseases and may lead to new kinds of vaccines,” said Elad Sharon, M.D., M.P.H., of NCI‘s Division of Cancer Treatment and Diagnosis. “For other applications, such as the treatment of cancer, research on mRNA vaccines also appears promising, but these approaches have not yet proven themselves.”
With findings starting to emerge from ongoing clinical trials of mRNA cancer vaccines, researchers could soon learn more about the safety and effectiveness of these treatments, Dr. Sharon added. Over the past 30 years, researchers have learned how to engineer stable forms of mRNA and deliver these molecules to the body through vaccines. Once in the body, the mRNA instructs cells that take up the vaccine to produce proteins that may stimulate an immune response against these same proteins when they are present in intact viruses or tumor cells. Among the cells likely to take up mRNA from a vaccine are dendritic cells, which are the sentinels of the immune system. After taking up and translating the mRNA, dendritic cells present the resulting proteins, or antigens, to immune cells such as T cells, starting the immune response.
“Dendritic cells act as teachers, educating T cells so that they can search for and kill cancer cells or virus-infected cells,” depending on the antigen, said Karine Breckpot, Ph.D., of the Vrije Universiteit Brussel in Belgium, who studies mRNA vaccines. The mRNA included in the Pfizer-BioNTech and the Moderna coronavirus vaccines instructs cells to produce a version of the “spike” protein that studs the surface of SARS-CoV-2. The immune system sees the spike protein presented by the dendritic cells as foreign and mobilizes some immune cells to produce antibodies and other immune cells to fight off the apparent infection. Having been exposed to the spike protein free of the virus, the immune system is now prepared, or primed, to react strongly to a subsequent infection with the actual SARS-CoV-2 virus.
Source: https://www.cancer.gov/
Categories: Uncategorized
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Tags: antibodies, antigens, cancer, cells, colorectal cancer, Dendritic cells, drugs, Food and Drug Administration, immune response, melanoma, Moderna, mRNA, NCI, pancreatic cancer, Pfizer-BioNTech, proteins, SARS-CoV-2 virus, spike protein, T-cells, tumor, tumors, vaccines, Vrije Universiteit Brussel
November 30, 2022
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An experimental therapeutic cancer vaccine induced two distinct and desirable immune system responses that led to significant tumor regression in mice. This is according to a new research study published in the journal Cell, reported by investigators from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).
According to the research findings, intravenous (IV) administration of the vaccine boosted the number of cytotoxic T cells capable of infiltrating and attacking tumor cells and engaged the innate immune system by inducing type I interferon. The innate immune response modified the tumor microenvironment, counteracting suppressive forces that otherwise would tamp down T-cell action. Modification of the tumor microenvironment was not found in mice that received the vaccine via subcutaneous administration (i.e. a needle injection into the skin).
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| Tags: cancer, cells, cytotoxic T cells, HPV, immune system, immunotherapeutic vaccines, IV, National Institute of Allergy and Infectious Diseases, National Institutes of Health, NIAID, NIH, papillomavirus, SNAPvax, tumor, type I interferon, Vaccine Research Center, Vaccitech North America, vax-innate, VRC
October 19, 2022
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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/
Categories: Uncategorized
| Tags: cancer cells, genetic code, immune system, Keytruda, melanoma, Merck, Moderna, mRNA vaccine, oncology, personalized vaccine, proteins, skin cancer, T-cells, tumor, virus
June 21, 2022
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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 ability – killing 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/
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https://newatlas.com/
Categories: Uncategorized
| Tags: brain cancer, EGFR, FGS, fluorescence, Fluorescence Guided Surgery, Glioblastoma, Institute of Cancer Research, light-activated, near-infrared light, photoimmunotherapy, protein, relapse, tumor
June 17, 2022
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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/
Categories: Uncategorized
| Tags: cancer, drug, healthy cells, IL-12, immune cells, immunotherapy drug, interleukin-12, lymphocytes, molecule, PME, side effects, tumor, tumor cells, University of Chicago
May 27, 2022
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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/
Categories: Uncategorized
| Tags: arterial plaques, arteries, blindness, blood clots, blood flow, cancer, cancerous cells, laser, laser angioplasty, microbubbles, tumor, ultrasound, University of Kansas, veins
April 15, 2022
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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, cells — innate 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/
Categories: Uncategorized
| Tags: advanced blood cancer, Affimed, Antibody, Hodgkin lymphoma, immune system cells, immunotherapy, lymphoma, MD Anderson, Natural Killer Cells, NK cells, protein, remission, stem cell, T cell, tumor, University of Texas MD Anderson Cancer Center
March 31, 2022
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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/
Categories: Uncategorized
| Tags: bacteria, Caltech, cancer cells, cancerous tumors, drugs, E.coli, escherichia coli, focused ultrasound, FUS, genes, immune system, Nissle 1917, therapeutic proteins, tumor, ultrasound
November 18, 2021
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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/
Categories: Uncategorized
| Tags: 3D-printed robotic animals, cancers, cells, chemotherapy drugs, drug nanoparticles, hydrogel 3D printed, iron oxide nanoparticles, magnetic, pH, tumor
November 15, 2021
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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/
AND
https://www.thebrighterside.news/
Categories: Uncategorized
| Tags: aggressive triple negative breast cancer, immune cells, immune system, immune-stimulating molecules, immunotherapy, Stanford, synthetic molecule, tumor, tumor cells, tumor-targeted immunotherapy
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