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/

Source: https://www.medicalnewstoday.com/

Rapid detection of the SARS-CoV-2 virus, in about 30 seconds following the test, has had successful preliminary results in Mano Misra’s lab at the University of Nevada, Reno. The test uses a nanotube-based electrochemical biosensor, a similar technology that Misra has used in the past for detecting tuberculosis and colorectal cancer as well as detection of biomarkers for food safety.

Professor Misra, in the University’s College of Engineering Chemical and Materials Department, has been working on nano-sensors for 10 years. He has expertise in detecting a specific biomarker in tuberculosis patients’ breath using a metal functionalized nano sensor.

Testing a nanotube-based electrochemical biosensor

“I thought that similar technology can be used to detect the SARS-CoV-2 virus, which is a folded protein,” Misra said. “

This is Point of Care testing to assess the exposure to COVID-19. We do not need a laboratory setting or trained health care workers to administer the test. Electrochemical biosensors are advantageous for sensing purposes as they are sensitive, accurate and simple.”

The test does not require a blood sample, it is run using a nasal swab or even exhaled breath, which has biomarkers of COVID-19. Misra and his team have successfully demonstrated a simple, inexpensive, rapid and non-invasive diagnostic platform that has the potential to effectively detect the SARS-CoV-2 virus.

The team includes Associate Professor Subhash Verma, virologist, and Research Scientist Timsy Uppal at the University’s School of Medicine, and Misra’s post-doctoral researcher Bhaskar Vadlamani.

“Our role on this project is to provide viral material to be used for detection by the nanomaterial sensor developed by Mano,” Verma said. “Mano contacted me back in April or May and asked whether we can collaborate to develop a test to detect SARS-CoV-2 infection by analyzing patients’ breath. That’s where we came in, to provide biological material and started with providing the surface protein of the virus, which can be used for detecting the presence of the virus.”

Source: https://www.unr.edu

Two German studies published today in JAMA Cardiology show abnormal heart imaging findings in recently recovered COVID-19 patients, and cardiac infections in those who have died from their infections.

The first, an observational cohort study, involved 100 unselected coronavirus patients identified from the University Hospital Frankfurt COVID-19 Registry from April to June, 57 risk factor-matched patients, and 50 healthy volunteers. Cardiac magnetic resonance (CMR) imaging revealed heart involvement in 78 patients and active cardiac inflammation in 60, independent of underlying conditions, disease severity, overall course of illness, and time from diagnosis to CMR.

Thirty-three of 100 patients required hospitalization. Detectable levels of high-sensitivity troponin were found in 71 COVID-19 patients, while significantly elevated levels were detected in five patients. Recovered COVID-19 patients had lower left ventricular ejection fraction, higher left ventricle volumes, higher left ventricle mass, and elevated native T1 and T2 than controls, all indicating heart dysfunction. Seventy-eight coronavirus patients had abnormal CMR findings, including 73 with raised myocardial native T1, 60 with raised myocardial native T2, 32 with myocardial late gadolinium enhancement, and 22 with pericardial enhancement, all signs of heart damage. Biopsy of the heart muscle in patients with serious findings showed ongoing immune-mediated inflammation.

The study authors noted that while most coronavirus research has focused on short-term respiratory complications, particularly in critically ill patients, mounting evidence suggests that COVID-19 has a significant impact on the cardiovascular system by worsening heart failure in patients with preexisting cardiac diseases. In this study, CMR revealed several kinds of heart abnormalities, each of which can be tied to underlying dysfunction and worse outcomes, the authors said. They added that their study also showed that direct tissue characterization with mapping measures on CMR is the most sensitive and clinically relevant way to detect early heart disease.

“While left and right ventricular ejection fraction were significantly reduced, there was a large overlap between patients recently recovered from COVID-19 and both control groups, demonstrating that volumes and function are inferior markers of disease detection,” they wrote.

The second study involved the autopsies of 39 COVID-19 patients conducted from Apr 8 to 18. Pathologists from the Legal Medicine at the University Medical Center Hamburg Eppendorf identified evidence of the COVID-19–causing SARS–CoV-2 virus—but not clinically relevant inflammation of the heart muscle—in 24 cadavers (61.5%), 16 (41.0%) of which had high loads of viral RNA.

Of the 24 cadavers with heart infections, a cytokine response panel showed that expression of six pro-inflammatory genes was higher in the 16 with high viral loads than in the 8 with low viral loads. But there were no signs of a massive influx of inflammatory cells into the heart muscle or tissue death in either group. Cause of death was listed as pneumonia in 35 cases (89.7%), while the other four (10.2%) died of necrotizing fasciitis, cardiac decompensation with previous heart failure, bacterial bronchitis, or unknown causes. The most common underlying illnesses were coronary artery disease (32 [82.0%]), high blood pressure (17 [43.6%]), and diabetes (7 [17.9%]). Median patient age was 85 years, and 23 of 39 patients (59%) were women.

“Overt fulminant myocarditis has been reported in isolated patients with SARS-CoV-2 infection,” the authors wrote. “However, the current data indicate that the presence of SARS-CoV-2 in cardiac tissue does not necessarily cause an inflammatory reaction consistent with clinical myocarditis.”

Source: https://www.cidrap.umn.edu/

Nanoparticles cloaked in human lung cell membranes and human immune cell membranes can attract and neutralize the SARS-CoV-2 virus in cell culture, causing the virus to lose its ability to hijack host cells and reproduce. The first data describing this new direction for fighting COVID-19 were published on June 17, 2020 in the journal Nano Letters. The “nanosponges” were developed by engineers at the University of California San Diego (UC San Diego) and tested by researchers at Boston University. The UC San Diego researchers call their nano-scale particles “nanosponges” because they soak up harmful pathogens and toxins.

In lab experiments, both the lung cell and immune cell types of nanosponges caused the SARS-CoV-2 virus to lose nearly 90% of its “viral infectivity” in a dose-dependent manner. Viral infectivity is a measure of the ability of the virus to enter the host cell and exploit its resources to replicate and produce additional infectious viral particles.

Instead of targeting the virus itself, these nanosponges are designed to protect the healthy cells the virus invades.

Nanosponges attacking and neutralizing the SARS-COV-2 virus

“Traditionally, drug developers for infectious diseases dive deep on the details of the pathogen in order to find druggable targets. Our approach is different. We only need to know what the target cells are. And then we aim to protect the targets by creating biomimetic decoys,” said Liangfang Zhang, a nanoengineering professor at the UC San Diego Jacobs School of Engineering.

His lab first created this biomimetic nanosponge platform more than a decade ago and has been developing it for a wide range of applications ever since. When the novel coronavirus appeared, the idea of using the nanosponge platform to fight it came to Zhang “almost immediately,” he said.

In addition to the encouraging data on neutralizing the virus in cell culture, the researchers note that nanosponges cloaked with fragments of the outer membranes of macrophages could have an added benefit: soaking up inflammatory cytokine proteins, which are implicated in some of the most dangerous aspects of COVID-19 and are driven by immune response to the infection.

Source: https://ucsdnews.ucsd.edu/