Data to be Presented at the 2021 Annual Meeting of the American Society for Clinical Oncology
Thursday, June 3, 2021
‘Next big wave’: Radiation drugs track and kill cancer cells
Doctors are reporting improved survival in men with advanced prostate cancer from an experimental drug that delivers radiation directly to tumor cells.
Few such drugs are approved now, but the approach may become a new way to treat patients with other hard-to-reach or inoperable cancers.
The study tested an emerging class of medicine called radiopharmaceuticals, drugs that deliver radiation directly to cancer cells. The drug in this case is a molecule that contains two parts: a tracker and a cancer-killing payload.
Trillions of these molecules hunt down cancer cells, latching onto protein receptors on the cell membrane. The payload emits radiation, which hits the tumor cells within its range.
“You can treat tumors that you cannot see. Anywhere the drug can go, the drug can reach tumor cells,” said Dr. Frank Lin, who had no role in the study but heads a division at the National Cancer Institute that helps develop such medicine.
Results were released Thursday by the American Society of Clinical Oncology ahead of its annual meeting this weekend. The study was funded by Novartis, the drug’s maker, which plans to seek approvals in the United States and Europe later this year.
When cancer is confined to the prostate, radiation can be beamed onto the body or implanted in pellets.
But those methods don’t work well in more advanced prostate cancer. About 43,000 men in the United States each year are diagnosed with prostate cancer that has spread and is no longer responding to hormone-blocking treatment.
The study tested a new way to get radiation treatment to such patients.
It involved 831 men with advanced prostate cancer. Two-thirds were given the radiation drug and the rest served as a comparison group. Patients got the drug through an IV every six weeks, up to six times.
After about two years, those who received the drug did better, on average. The cancer was kept at bay for nearly nine months compared to about three months for the others. Survival was better too — about 15 months versus 11 months.
The gain may not seem like much, but “these patients don’t have many options,” said ASCO president Dr. Lori Pierce, a cancer radiation specialist at the University of Michigan.
Radioactivity can reduce blood cell production, which can lead to anemia and clotting problems for patients. In the study, 53% of the patients had serious side effects compared to 38% of patients in the comparison group. Both groups were allowed to get other treatments.
The results pave the way for government approval and will boost interest in radiation drugs, Lin said.
Others already in use include Novartis’ Lutathera for a rare type of cancer of the stomach and gut.
And Bayer’s Xofigo is approved for men whose prostate cancer has spread to the bone but not elsewhere. Xofigo targets areas where the body is trying to repair bone loss from tumor damage, but it isn’t directly aimed at prostate cancer cells wherever they may be in the body.
Since the experimental drug targets tumor cells, “that would be a first for prostate cancer,” Lin said.
In the coming decade, such drugs “will be a major thrust of cancer research,” said Dr. Charles Kunos, who worked on standards for radiopharmaceutical research at the National Cancer Institute before leaving to join University of Kentucky’s Markey Cancer Center. “It will be the next big wave of therapeutic development.”
“There’s great potential” with drugs being tested for melanoma and breast, pancreatic and other cancers, said Dr. Mary-Ellen Taplin of Dana-Farber Cancer Institute in Boston, who enrolled patients in the study and reviewed the data.
As for prostate cancer, “it opens up a range of future strategies,” including at earlier stages of disease and alongside other treatments, said study leader Dr. Michael Morris of Memorial Sloan Kettering Cancer Center in New York.
https://apnews.com/article/cancer-science-business-health-54e08ed1a440669a88932aba505d2e54
Senseonics Study: Strong Accuracy of 180 Day CGM Sensor
Senseonics Holdings, Inc. (NYSE-American: SENS), a medical technology company focused on the development and commercialization of the first and only long-term, implantable continuous glucose monitoring (CGM) system – the Eversense® CGM System – today announced the results of the PROMISE Study evaluating the accuracy and safety of the next generation Eversense CGM System for up to 180 days with reduced calibrations. The data was presented by Satish Garg, MD, Professor of Medicine at the Barbara Davis Center of the University of Colorado, Denver, and the study group Principal Investigator (PI), as an oral presentation at the 14th Annual ATTD Meeting. Results were presented for both the primary sensor and for a secondary sensor with modified chemistry (referred to as the SBA sensor) in a subset of study participants.
Metal ions help COVID-19 virus to disguise itself
Scientists from The University of Texas Health Science Center at San Antonio have discovered a mechanism by which SARS-CoV-2 exploits changes in metal ion concentrations to disguise itself in the body. Varying concentrations of metal ions -- positively charged atoms such as magnesium, manganese and calcium -- are observed in hospitalized COVID-19 patients.
"This is a newly described metal-dependent mechanism by which these ions help the virus to evade immune surveillance," said Yogesh Gupta, PhD, senior author of the research published June 2 in the journal Nature Communications. Dr. Gupta is assistant professor of biochemistry and structural biology at the UT Health Science Center San Antonio and investigator with its Greehey Children's Cancer Research Institute.
Dr. Gupta and colleagues captured atomic-level snapshots during various stages of camouflaging activity of the coronavirus. It turns out metal ions have an architectural purpose -- they form a bridge between viral messenger RNA (which are instructions for encoding the virus) and a protein complex consisting of viral proteins nsp16 and nsp10. The activity is sort of like a scaffold swaying in the wind and workers laying hands on it to steady it.
With the scaffold stabilized, the virus then uses nsp16 to modify its messenger RNA cap into a Trojan horse unrecognizable to the immune system. This tricks the defenses, protects the RNA code from being degraded and enhances viral growth in the body. This activity is required each time the virus multiplies.
The nsp16/nsp10 protein complex stretches itself when the RNA cap is modified, which is a second finding the scientists reported. The stretching is facilitated by metal ion binding.
The understandings gleaned in this research can eventually aid treatment of all coronaviruses.
"The next step is to use this structural knowledge to develop novel therapies to treat COVID-19 and emerging coronavirus infections," Dr. Gupta said. "We are already studying how imbalances in metal concentrations regulate the host immune response to these infections."
###
This research was made possible by the San Antonio Partnership for Precision Therapeutics, the Institute for Integration of Medicine and Science, the Max and Minnie Tomerlin Voelcker Fund, the Cancer Prevention and Research Institute of Texas, UT Health San Antonio and the Greehey Children's Cancer Research Institute.
A metal ion orients SARS-CoV-2 mRNA to ensure accurate 2'-O methylation of its first nucleotide
Thiruselvam Viswanathan, Anurag Misra, Siu-Hong Chan, Shan Qi, Nan Dai, Shailee Arya, Luis Martinez-Sobrido, Yogesh K. Gupta
First published: June 2, 2021, Nature Communications
https:/
https://www.eurekalert.org/pub_releases/2021-06/uoth-mih060221.php
Why Adamis Shares Are Ripping Higher Today
Shares of Adamis Pharmaceuticals Corporation
ADMP 49.86% spiked higher in afternoon trading Thursday following some positive tidings on one of its pipeline assets.
What Happened: Study of cell cultures by researchers at the National Institutes of Health showed that experimental drug Tempol may be a promising oral antiviral treatment.
Tempol has been licensed by Adamis and is being evaluated as a treatment option for respiratory diseases, including asthma, respiratory syncytial virus, influenza and COVID-19.
"An oral drug that prevents SARS-CoV-2 from replicating would be an important tool for reducing the severity of the disease," said Diana Bianchi, Director at the National Institute of Child Health and Human Development.
In cell culture experiments with live SARS-CoV-2 virus, the team found that the drug can inhibit viral replication. Tempol doses used in NIH's antiviral experiments could likely be achieved in tissues that are primary targets for the virus, such as the salivary glands and the lungs, the study showed.
The study team plans on conducting additional animal studies and will seek opportunities to evaluate Tempol in a clinical study of COVID-19.
Adamis' Progress With Tempol In COVID-19: Adamis submitted an investigational new drug application for Tempol to the FDA for evaluating the use of it for COVID-19 treatment at the start of the year, and the IND application was cleared by the FDA in February.
Tuesday, the company said in its earnings release, it's working with a large clinical research organization that has started the key operational aspects of the clinical study including site selection, site agreements, and vendor agreements.
Adamis is a biopharma developing and commercializing specialty products for respiratory disease, allergy and opioid overdose.
https://www.benzinga.com/general/biotech/21/06/21417241/why-adamis-shares-are-ripping-higher-today
Explaining low oxygen levels in COVID-19 patients
A new study published in the journal Stem Cell Reports by University of Alberta researchers is shedding light on why many COVID-19 patients, even those not in hospital, are suffering from hypoxia -- a potentially dangerous condition in which there is decreased oxygenation in the body's tissues. The study also shows why the anti-inflammatory drug dexamethasone has been an effective treatment for those with the virus.
"Low blood-oxygen levels have been a significant problem in COVID-19 patients," said study lead Shokrollah Elahi, associate professor in the Faculty of Medicine & Dentistry. "Because of that, we thought one potential mechanism might be that COVID-19 impacts red blood cell production."
In the study, Elahi and his team examined the blood of 128 patients with COVID-19. The patients included those who were critically ill and admitted to the ICU, those who had moderate symptoms and were admitted to hospital, and those who had a mild version of the disease and only spent a few hours in hospital. The researchers found that, as the disease became more severe, more immature red blood cells flooded into blood circulation, sometimes making up as much as 60 per cent of the total cells in the blood. By comparison, immature red blood cells make up less than one per cent, or none at all, in a healthy individual's blood.
"Immature red blood cells reside in the bone marrow and we do not normally see them in blood circulation," Elahi explained. "This indicates that the virus is impacting the source of these cells. As a result, and to compensate for the depletion of healthy immature red blood cells, the body is producing significantly more of them in order to provide enough oxygen for the body."
The problem is that immature red blood cells do not transport oxygen -- only mature red blood cells do. The second issue is that immature red blood cells are highly susceptible to COVID-19 infection. As immature red blood cells are attacked and destroyed by the virus, the body is unable to replace mature red blood cells -- which only live for about 120 days -- and the ability to transport oxygen in the bloodstream is diminished.
The question was how the virus infects the immature red blood cells. Elahi, known for his prior work demonstrating that immature red blood cells made certain cells more susceptible to HIV, began by investigating whether the immature red blood cells have receptors for SARS-CoV-2. After a series of studies, Elahi's team was the first in the world to demonstrate that immature red blood cells expressed the receptor ACE2 and a co-receptor, TMPRSS2, which allowed SARS-CoV-2 to infect them.
Working in conjunction with the the lab of virologist Lorne Tyrrell at the U of A's Li Ka Shing Institute of Virology, the team performed investigative infection testing with immature red blood cells from COVID-19 patients and proved these cells got infected with the SARS-CoV-2 virus.
"These findings are exciting but also show two significant consequences," Elahi said. "First, immature red blood cells are the cells being infected by the virus, and when the virus kills them, it forces the body to try to meet the oxygen supply requirements by pumping more immature red blood cells out of the bone marrow. But that just creates more targets for the virus.
"Second, immature red blood cells are actually potent immunosuppressive cells; they suppress antibody production and they suppress T-cell immunity against the virus, making the entire situation worse. So in this study, we have demonstrated that more immature red blood cells means a weaker immune response against the virus."
Following the discovery that immature red blood cells have receptors that allow them to become infected by the coronavirus, Elahi's team then began testing various drugs to see whether they could reduce immature red blood cells' susceptibility to the virus.
"We tried the anti-inflammatory drug dexamethasone, which we knew helped to reduce mortality and the duration of the disease in COVID-19 patients, and we found a significant reduction in the infection of immature red blood cells," said Elahi.
When the team began exploring why dexamethasone had such an effect, they found two potential mechanisms. First, dexamethasone suppresses the response of the ACE2 and TMPRSS2 receptors to SARS-CoV-2 in immature red blood cells, reducing the opportunities for infection. Second, dexamethasone increases the rate at which the immature red blood cells mature, helping the cells shed their nuclei faster. Without the nuclei, the virus has nowhere to replicate.
Luckily, putting Elahi's findings into practice doesn't require significant changes in the way COVID-19 patients are being treated now.
"For the past year, dexamethasone has been widely used in COVID-19 treatment, but there wasn't a good understanding as to why or how it worked," Elahi said. "So we are not repurposing or introducing a new medication; we are providing a mechanism that explains why patients benefit from the drug."
Elahi noted that Wendy Sligl and Mohammed Osman had a crucial role in recruiting COVID-19 patients for the study. The research was supported by Fast Grants, the Canadian Institutes of Health Research and a grant from the Li Ka Shing Institute of Virology.
Story Source:
Materials provided by University of Alberta Faculty of Medicine & Dentistry. Original written by Ryan O'Byrne. Note: Content may be edited for style and length.
Journal Reference:
- Shima Shahbaz, Lai Xu, Mohammed Osman, Wendy Sligl, Justin Shields, Michael Joyce, D. Lorne Tyrrell, Olaide Oyegbami, Shokrollah Elahi. Erythroid precursors and progenitors suppress adaptive immunity and get invaded by SARS-CoV-2. Stem Cell Reports, 2021; 16 (5): 1165 DOI: 10.1016/j.stemcr.2021.04.001
Secondary infections inflame the brain, worsening cognition in Alzheimer's
New research into Alzheimer's disease (AD) suggests that secondary infections and new inflammatory events amplify the brain's immune response and affect memory in mice and in humans -- even when these secondary events occur outside the brain.
Scientists believe that key brain cells (astrocytes and microglia) are already in an active state due to inflammation caused by AD and this new research shows that secondary infections can then trigger an over-the-top response in those cells, which has knock-on effects on brain rhythms and on cognition.
In the study, just published in Alzheimer's & Dementia, the journal of the Alzheimer's Association, mice engineered to show features of AD were exposed to acute inflammatory events to observe the downstream effects on brain inflammation, neuronal network function and memory.
These mice showed new shifts in the output of astrocytes and microglia and displayed new cognitive impairment and disturbed 'brain rhythms' that did not occur in healthy, age-matched, mice. These new onset cognitive changes are similar to acute and distressing psychiatric disturbances like delirium, that frequently occur in elderly patients.
Although it is difficult to replicate these findings in patients, the study additionally showed that AD patients who died with acute systemic infection showed heighted brain levels of IL-1β -- a pro-inflammatory molecule that was important in causing the heightened immune response and the new onset disruptions seen in the AD mice.
Colm Cunningham, Associate Professor in Trinity's School of Biochemistry and Immunology, and the Trinity Biomedical Sciences Institute, led the research. He said:
"Alzheimer's disease is the most common form of dementia, affecting more than 5% of those over 60 and this distressing, debilitating condition causes difficulties for a huge number of people across the globe. The more we know about the disease and its progression the better chance we have of treating those living with it. We believe our work adds to this knowledge base in a few ways. Primarily, we show that the Alzheimer's-affected brain has a greater vulnerability to acute inflammatory events, even if they occur outside the brain.
Placing this within the context of the slowly evolving progression of AD, we propose that these hypersensitive responses, now seen in multiple cell populations, may contribute to the negative outcomes that follow acute illness in older patients, including episodes of delirium and the accelerated cognitive trajectory that has been observed in patients who experience delirium before or during their dementia."
The research was supported by the US National Institutes of Health (NIH) and by the Wellcome Trust.
Story Source:
Materials provided by Trinity College Dublin. Note: Content may be edited for style and length.
Journal Reference:
- Ana Belen Lopez-Rodriguez, Edel Hennessy, Carol L. Murray, Arshed Nazmi, Hugh J. Delaney, Dáire Healy, Steven G. Fagan, Michael Rooney, Erika Stewart, Anouchka Lewis, Niamh de Barra, Philip Scarry, Louise Riggs-Miller, Delphine Boche, Mark O. Cunningham, Colm Cunningham. Acute systemic inflammation exacerbates neuroinflammation in Alzheimer's disease: IL-1β drives amplified responses in primed astrocytes and neuronal network dysfunction. Alzheimer's and Dementia, 2021 DOI: 10.1002/alz.12341
Subscribe to:
Posts (Atom)