Ultrasound guides supercharged immune cells to only attack cancer

Bioengineers at the University of California San Diego have developed a cancer immunotherapy that pairs ultrasound with cancer-killing immune cells to destroy malignant tumors while sparing normal tissue. The new experimental therapy significantly slowed down the growth of solid cancerous tumors in mice. The team, led by the labs of UC San Diego bioengineering professor Peter Yingxiao Wang and bioengineering professor emeritus Shu Chien, detailed their work in a paper published Aug. 12 in Nature Biomedical Engineering.

The work addresses a longstanding problem in the field of cancer immunotherapy: how to make chimeric antigen receptor (CAR) T-cell therapy safe and effective at treating solid tumors. CAR T-cell therapy is a promising new approach to treat cancer. It involves collecting a patient’s T cells and genetically engineering them to express special receptors, called CAR, on their surface that recognize specific antigens on cancer cells. The resulting CAR T cells are then infused back into the patient to find and attack cells that have the cancer antigens on their surface.

This therapy has worked well for the treatment of some blood cancers and lymphoma, but not against solid tumors. That’s because many of the target antigens on these tumors are also expressed on normal tissues and organs. This can cause toxic side effects that can kills cells—these effects are known as on-target, off-tumor toxicity.

CAR T cells are so potent that they may also attack normal tissues that are expressing the target antigens at low levels,” said first author Yiqian (Shirley) Wu, a project scientist in Wang’s lab.

The problem with standard CAR T cells is that they are always on—they are always expressing the CAR protein, so you cannot control their activation,” explained Wu.

To combat this issue, the team took standard CAR T cells and re-engineered them so that they only express the CAR protein when ultrasound energy is applied. This allowed the researchers to choose where and when the genes of CAR T cells get switched on.

We use ultrasound to successfully control CAR T cells directly in vivo for cancer immunotherapy,” said Wang, who is a faculty member of the Institute of Engineering in Medicine and the Center for Nano-ImmunoEngineering, both at UC San Diego. What’s exciting about the use of ultrasound, noted Wang, is that it can penetrate tens of centimeters beneath the skin, so this type of therapy has the potential to non-invasively treat tumors that are buried deep inside the body.

The team’s approach involves injecting the re-engineered CAR T cells into tumors in mice and then placing a small ultrasound transducer on an area of the skin that’s on top of the tumor to activate the CAR T cells. The transducer uses what’s called focused ultrasound beams to focus or concentrate short pulses of ultrasound energy at the tumor. This causes the tumor to heat up moderately—in this case, to a temperature of 43 degrees Celsius (109 degrees Fahrenheit)—without affecting the surrounding tissue. The CAR T cells in this study are equipped with a gene that produces the CAR protein only when exposed to heat. As a result, the CAR T cells only switch on where ultrasound is applied.

The research was published in the journal Nature Biomedical Engineering.

Covid-19: Type O blood Divides By 2 The Risk Of Intubation

Research is coalescing around the idea that people with Type O blood may have a slight advantage during this pandemicTwo studies published this week suggest that people with Type O have a lower risk of getting the coronavirus, as well as a reduced likelihood of getting severely sick if they do get infected. One of the new studies specifically found that COVID-19 patients with Type O or B blood spent less time in an intensive-care unit than their counterparts with Type A or AB. They were also less likely to require ventilation and less likely to experience kidney failure.

These new findings echo similar findings about Type O blood seen in previous research, creating a clearer picture of one particular coronavirus risk factor. Both new studies came out Wednesday in the journal Blood AdvancesOne looked at 95 critically ill COVID-19 patients at hospitals in Vancouver, Canada, between February and April. They found that patients with Type O or B blood spent, on average, 4.5 fewer days in the intensive-care unit than those with Type A or AB blood. The latter group stayed, on average, 13.5 days in the ICU. The researchers did not see any link between blood type and the patient’s total hospital stay, however. They did, however, find that only 61 percent of the patients with Type O or B blood required a ventilator, compared to 84 percent of patients with Type A or AB.

Patients with Type A or AB, meanwhile, were also more likely to need dialysis, a procedure that helps the kidneys filter toxins from the blood.

“Patients in these two blood groups may have an increased risk of organ dysfunction or failure due to COVID-19 than people with blood types O or B,” the study authors concluded.

A June study found a similar link: Patients in Italy and Spain with Type O blood had a 50 percent reduced risk of severe coronavirus infection (meaning they needed intubation or supplemental oxygen) compared to patients with other blood types.

The second new study found that people with Type O blood may be at a lower risk of getting he coronavirus in the first place relative to people with other blood types. The team examined nearly half a million people in the Netherlands who were tested for COVID-19 between late February and late July. Of the roughly 4,600 people who tested positive and reported their blood type, 38.4 percent had Type O blood. That’s lower than the prevalence of Type O in a population of 2.2 million Danish people, 41.7 percent, so the researchers determined that people with Type O blood had disproportionately avoided infection. “Blood group O is significantly associated with reduced susceptibility,” the authors wrote.

In general, your blood type depends on the presence or absence of proteins called A and B antigens on the surface of red blood cells – a genetic trait inherited from your parents. People with O blood have neither antigen. It’s the most common blood type: About 48 percent of Americans have Type O bloodaccording to the Oklahoma Blood Institute.

The new studies about blood type and coronavirus risk align with prior research on the topic. A study published in July found that people with Type O were less likely to test positive for COVID-19 than those with other blood types. An April study, too, (though it has yet to be peer-reviewed) found that among 1,559 coronavirus patients in New York City, a lower proportion than would be expected had Type O blood.

And in March, a study of more than 2,100 coronavirus patients in the Chinese cities of Wuhan and Shenzhen also found that people with Type O blood had a lower risk of infection.

Past research has also suggested that people with Type O blood were less susceptible to SARS, which shares 80 percent of its genetic code with the new coronavirusA 2005 study in Hong Kong found that most individuals infected with SARS had non-O blood types. Despite this growing body of evidence, however, Mypinder Sekhon, a co-author of the Vancouver study, said the link is still tenuous.

I don’t think this supersedes other risk factors of severity like age and comorbidities and so forth,” he told CNN, adding, “if one is blood group A, you don’t need to start panicking. And if you’re blood group O, you’re not free to go to the pubs and bars.”

Source: https://www.businessinsider.com/

‘Game Changing’ 15-Minute Covid-19 Test Cleared in Europe

Becton Dickinson and Co.’s Covid-19 test that returns results in 15 minutes has been cleared for use in countries that accept Europe’s CE marking, the diagnostics maker said Wednesday. The test is part of a new class of quicker screening tools named for the identifying proteins called antigens they detect on the surface of SARS-CoV-2. Becton Dickinson expects to begin selling the test, which runs on the company’s cellphone-sized BD Veritor Plus System, in European markets at the end of October. It will likely be used by emergency departments, general practitioners and pediatricians.

Becton Dickinson said its antigen assay is 93.5% sensitive, a measure of how often it correctly identifies infections, and 99.3% specific, the rate of correct negative tests. The data, which differ from the U.S. label’s 84% sensitivity and 100% specificity, come from a new clinical study that was recently submitted to the U.S.  , spokesman Troy Kirkpatrick said.

https://www.bloomberg.com/

How Gene-edited White Blood Cells Are Helping Fight Cancer

For the first time in the United States, a gene editing tool has been used to treat advanced cancer in three patients and showed promising early results in a pilot phase 1 clinical trial. So far the treatment appears safe, and more results are expected soon. To develop a safer and more effective treatment for cancer patients, scientists from the University of Pennsylvania, the Parker Institute for Cancer Immunotherapy in San Francisco and Tmunity Therapeutics, a biotech company in Philadelphia, developed an advanced version of immunotherapy. In this treatment, a patient’s own immune cells are removed from the body, trained to recognize specific cancer cells and then finally injected back into the patient where they multiply and destroy them.

Unlike chemotherapy or radiation therapy, which directly kills cancer cells, immunotherapy activates the body’s own immune system to do the work. This team used a gene editing tool called CRISPR to alter immune cells, turning them into trained soldiers to locate and kill cancer cells. By using this technique, the team hoped to develop a more effective form of immunotherapy with minimal side effects.

Better CRISPR-based gene editors for the diagnosis and treatment of cancer and other disorders, . combining chemistry, biology and nanotechnology, are used to engineer, control and deliver gene editing tools more efficiently and precisely.

The first step in making these tumor-killing cells used in the cancer drug trial was to isolate the T-cells – a type of white blood cells that fights pathogens and cancer cells – from the blood of the cancer patients. Two patients with advanced multiple myeloma and one patient with myxoid/round cell liposarcomav were enrolled for this study.

To arm the T-cells and bolster their tumor-fighting skills without harming normal cells, scientists genetically engineered the T-cellsdisabling three genes and adding one gene – before returning them to the patients.

The first two of these deleted genes encode T-cell receptors, which are proteins found on the surface of the T-cells that can recognize and bind specific molecules, known as antigens, on cancer cells. When these engineered T-cells bind to these antigens, it allows them to attack and directly kill the cancer cells. But the problem is that a single T-cell can recognize multiple different antigens in the body, making them less focused on finding the cancer cells. By eliminating these two genes, the T-cells are less likely to attack the wrong target or the host, a phenomenon called autoimmunity, In addition, they disrupted a third gene, called programmed cell death protein 1, which slows down the immune response. Disabling the programmed cell death protein 1 gene improves the efficiency of T-cells.

The final step in the transformation of these cells was adding a gene which produces a new T-cell receptor that recognizes and grabs onto a specific marker on the cancer cells called NY-ESO-1. With three genes deleted and one added, the T-cells are now ready to fight cancer.

Source: https://theconversation.com/