Category: biotech

Their profile of the oncologist from Boston’s Dana-Farber Cancer Institute notes Dr. Wu’s research “has laid the scientific foundation for the development of cancer vaccines tailored to the genetic makeup of an individual’s tumor.”

It’s a strategy looking increasingly promising for some hard-to-treat cancers such as melanoma and pancreatic cancer, according to the results of early-stage trials, and may ultimately be widely applicable to many of the 200 or so forms of cancer…

The most common treatments for cancer — radiation therapy and chemotherapy — are like sledgehammers, striking all cells and often damaging healthy tissue. Since the 1950s, cancer researchers have been seeking a way to dial up the body’s immune system, which naturally tries to fight cancer but is outsmarted by it, to attack tumor cells. Progress on that front was middling until about 2011 with the arrival of a class of drugs called checkpoint inhibitors, which boost the anti-tumor activity of T cells, an important part of the immune system… These drugs have helped some people with cancer who would have been given months to live survive for decades, but they don’t work for all cancer patients, and researchers continue to look for ways to turbocharge the body’s immune system against cancer…

Wu’s research focused on small mutations in cancer tumor cells. These mutations, which occur as the tumor grows, create proteins that are slightly different to those in healthy cells. The altered protein generates what’s called a tumor neoantigen that can be recognized by the immune system’s T cells as foreign, and therefore susceptible to attack. With thousands of potential neoantigen candidates, Wu used “tour de force lab work” to identify the neoantigens that are on the cell surface, making them a potential target for a vaccine, said Urban Lendahl, professor of genetics at the Karolinska Institutet in Sweden and the secretary of the committee that awarded the prize. “If the immune system is to have a chance to attack the tumor, this difference must be manifested on the surface of the tumor cells. Otherwise, it’s pretty pointless,” Lendahl added…

By sequencing DNA from healthy and cancer cells, Wu and her team identified a cancer patient’s unique tumor neoantigens. Synthetic copies of these unique neoantigens could be used as a personalized vaccine to activate the immune system to target the cancer cells… Once it had FDA approval, the team vaccinated six patients with advanced melanoma with a seven-shot course of patient-specific neoantigens vaccines. The breakthrough results were published in an 2017 article in Nature. For some patients, this treatment resulted in the immune system’s cells being activated and targeting the tumor cells. The results, along with another paper published the same year led by the founders of mRNA vaccine company BioNTech, provided “proof of principle” that a vaccine can be targeted to a person’s specific tumor, Lendahl said.

A follow-up by Wu’s team four years after the patients received the vaccines published in 2021, showed that the immune responses were effective in keeping cancer cells under control… Since then, Wu’s team, other groups of medical researchers and pharmaceutical companies, including Merck, Moderna and BioNTech, have further developed this field of research, with trials underway for vaccines that treat pancreatic and lung cancer as well as melanoma.

“All the trials underway are small-scale, typically involving a handful of patients with later-stage disease and a high tolerance for safety risks,” adds CNN.

“To show that these type of cancer vaccines work, much larger randomized control trials are needed.”

From the article:

Typically, cancer cells evade a person’s immune system because it is recognized as that person’s cells. Wagner developed a tumor lysate particle only (TLPO) vaccine that uses a person’s tumor cells to identify particular parts that are then presented back in the body using the vaccine in a way that can stimulate their immune system to gain the ability to detect these cancer cells like an infection, allowing the immune system to fight the cancer itself.

“People used to ask me the question, ‘When will there be a cure for cancer?’ And I’ve been doing this for 60 years and I could never answer that question,” Wagner said. “Until recently, until the last three or four or five years.” Wagner believes this type of cancer treatment could be a key to finding the long-awaited cure for cancer, all cancers, if paired with early detection.

Wagner’s TLPO cancer vaccine has been tested in hundreds of patients with advanced forms of melanoma in Phase 2 clinical trials. The most recent data presented at an academic conference showed nearly 95% of people given only the vaccine were still alive three years after starting treatment and 64% were still disease-free. Among the most advanced forms of melanoma, disease-free survival after three years for people with stage III disease was 60% in the vaccine-only group, compared to about 39% in the placebo group. Disease-free survival for those with stage IV disease was about 68% in the vaccine-only group, and zero in the placebo group.

The most common side effects were redness or pain at the injection site, fever and fatigue after the injection – similar to other vaccines that stimulate an immune response.

Based on this data and other studies, the U.S. Food and Drug Administration has greenlit Wagner’s vaccine to start a Phase 3 clinical trial. It will be a three-year endeavor with a goal to enroll 500 people and is planned to launch sometime this year, Riley Polk, president of Orbis Health Solutions, told WLOS, an ABC News affiliate in Asheville, North Carolina.

Polk’s own father was told there were no treatment options left for his lung cancer, according to the article. That was more than 10 years ago, and “His father opted to try Wagner’s cancer vaccine and lived 10 more years before dying from something unrelated to cancer.” Polk gives ABC News this quote.

“You can tell me a lot of things, but you can’t tell me [the vaccine] doesn’t work.”

For a time, Wall Street went vegetarian. In 2019 Beyond Meat was valued at over $10 billion, more than Macy’s or Xerox. The most bullish investors believed that plant-based meat would make up 15% of all meat sales by 2030. But the reality of Americans’ interest in plant-based meat has proven more complicated than investors thought, and the adoption of meat alternatives has been slower than what was once hoped. Today Beyond Meat is valued at just over $900 million. The sobering story is similar to those experienced by many new ventures that see exhilarating hype after a flood of Silicon Valley venture capital cash, fueled by excitement about innovation. Bill Gates backed Beyond Meat, and a number of venture capital firms that typically invest in tech startups funneled money to startups making plant-based meat. Even the meat industry’s biggest players have, ironically, invested in companies coming up with plant-based meat. While eating plant-based meat (or no meat at all) has been shown to be the most effective thing individual consumers can do to fight climate change, “consumers seem hesitant to adapt their behavior when the environment — not their health or wallets — is the sole beneficiary,” reports The Guardian. “Despite the increasing alarm over climate change, the number of Americans who are vegetarian or vegan has remained relatively stable over the last 20 years.”

“Even when participants in a study conducted at Purdue University in Indiana were given information about the carbon footprint of meat production, participants were more likely to go with regular meat over a plant-based alternative.”

Despite the positive results, questions remain about whether therapies based on Crispr will work safely and effectively, analysts said. Intellia’s latest studies involved a small number of patients, and were disclosed in news releases and haven’t been published in a peer-reviewed journal. The NTLA-2002 study results were presented at the Bradykinin Symposium in Berlin, a medical meeting focused on angioedema. The data came from small, so-called Phase 1 studies conducted in New Zealand and the U.K. that didn’t include control groups. Results from such early studies can be unreliable predictors of a drug’s safety and effectiveness once the compound is tested in larger numbers of patients. The findings, nevertheless, add to preliminary but promising evidence of the potential for drugs based on the gene-editing technology. Last year, Intellia said that NTLA-2001 reduced the disease-causing protein involved in ATTR patients.

Now a new design by MIT engineers “might make the technology as wearable and accessible as buying Band-Aids at the pharmacy.”
In a paper appearing today in Science, the engineers present the design for a new ultrasound sticker — a stamp-sized device that sticks to skin and can provide continuous ultrasound imaging of internal organs for 48 hours.

The researchers applied the stickers to volunteers and showed the devices produced live, high-resolution images of major blood vessels and deeper organs such as the heart, lungs, and stomach. The stickers maintained a strong adhesion and captured changes in underlying organs as volunteers performed various activities, including sitting, standing, jogging, and biking….
From the stickers’ images, the team was able to observe the changing diameter of major blood vessels when seated versus standing. The stickers also captured details of deeper organs, such as how the heart changes shape as it exerts during exercise. The researchers were also able to watch the stomach distend, then shrink back as volunteers drank then later passed juice out of their system. And as some volunteers lifted weights, the team could detect bright patterns in underlying muscles, signaling temporary microdamage.

“With imaging, we might be able to capture the moment in a workout before overuse, and stop before muscles become sore,” says Chen. “We do not know when that moment might be yet, but now we can provide imaging data that experts can interpret.”

They’re already envisioning other possibilities:
If the devices can be made to operate wirelessly — a goal the team is currently working toward — the ultrasound stickers could be made into wearable imaging products that patients could take home from a doctor’s office or even buy at a pharmacy. “We envision a few patches adhered to different locations on the body, and the patches would communicate with your cellphone, where AI algorithms would analyze the images on demand,” says the study’s senior author, Xuanhe Zhao, professor of mechanical engineering and civil and environmental engineering at MIT.

“We believe we’ve opened a new era of wearable imaging: With a few patches on your body, you could see your internal organs.”

In New Zealand, where Verve’s clinical trial is taking place, doctors will give the gene treatment to 40 people who have an inherited form of high cholesterol known as familial hypercholesterolemia, or FH. People with FH can have cholesterol readings twice the average, even as children. Many learn they have a problem only when they get hit with a heart attack, often at a young age. The study also marks an early use of base editing, a novel adaptation of CRISPR that was first developed in 2016. Unlike traditional CRISPR, which cuts a gene, base editing substitutes a single letter of DNA for another.

The gene Verve is editing is called PCSK9. It has a big role in maintaining LDL levels and the company says its treatment will turn the gene off by introducing a one-letter misspelling. […] One reason Verve’s base-editing technique is moving fast is that the technology is substantially similar to mRNA vaccines for covid-19. Just like the vaccines, the treatment consists of genetic instructions wrapped in a nanoparticle, which ferries everything into a cell. While the vaccine instructs cells to make a component of the SARS-CoV-2 virus, the particles in Verve’s treatment carry RNA directions for a cell to assemble and aim a base-editing protein, which then modifies that cell’s copy of PCSK9, introducing the tiny mistake. In experiments on monkeys, Verve found that the treatment lowered bad cholesterol by 60%. The effect has lasted more than a year in the animals and could well be permanent. The report notes that the human experiment does carry some risk. “Nanoparticles are somewhat toxic, and there have been reports of side effects, like muscle pain, in people taking other drugs to lower PCSK9,” reports MIT Technology Review. “And whereas treatment with ordinary drugs can be discontinued if problems come up, there’s as yet no plan to undo gene editing once it’s performed.”

“Now, over two decades later, MIT Professor Jonathan Weissman and colleagues have gone beyond the sequence to present the first comprehensive functional map of genes that are expressed in human cells.”
The data from this project, published online June 9 in Cell, ties each gene to its job in the cell, and is the culmination of years of collaboration on the single-cell sequencing method Perturb-seq.

The data are available for other scientists to use. “It’s a big resource in the way the human genome is a big resource, in that you can go in and do discovery-based research,” says Weissman, who is also a member of the Whitehead Institute and an investigator with the Howard Hughes Medical Institute….

“I think this dataset is going to enable all sorts of analyses that we haven’t even thought up yet by people who come from other parts of biology, and suddenly they just have this available to draw on,” says former Weissman Lab postdoc Tom Norman, a co-senior author of the paper.

The announcement credits the single-sequencing tool Perturb-seq and CRISPR-Cas9 genome editing which introduced genetic changes into cells and then captured information about which RNAs expressed (uses single-cell RNA sequencing).

The researchers scaled the method to the entire genome using human blood cancer cell lines and noncancerous cells derived from the retina, ultimately using Perturb-seq across more than 2.5 million cells.

Thanks to Slashdot reader Hmmmmmm for sharing the news.

They have not stated the cause of the spill. “Spill investigators and scientists took a look at the area Jan. 18-19 and saw iron staining in the tributary channel consistent with a low pH environment,” reports local news station KXAN, citing the memo. “WPD says it was in this tributary stretch from the Samsung plant to the main branch of Harris Branch Creek that WPD staff found no surviving aquatic life, including fish.”

Holmes took the witness stand for more than 20 hours to defend herself. She accused her ex-boyfriend and former deputy at Theranos, Ramesh “Sunny” Balwani, of sexual abuse, saying that clouded her sense of judgement. Balwani faces a separate fraud trial in the same court in February. Holmes also showed remorse on the stand. She said she wished she had handled some key business matters differently. But she blamed others for the downfall of Theranos. She said lab directors whom she had trusted were the ones closest to the technology. And she said Balwani, not her, oversaw the company’s financial forecasts, which were later discovered to be grossly inflated. Yet the government offered evidence that Holmes had an iron grip on Theranos’ operations. Prosecutors argued she did not stop — and even helped spread — falsehoods about the company that misled investors into pouring millions into the startup. Theranos’ value, once estimated at more than $9 billion, was ultimately squandered.