Research using non-toxic bacteria to fight high-mortality cancers prepares for clinical trials

 A University of Massachusetts Amherst-Ernest Pharmaceuticals team of scientists has made "exciting," patient-friendly advances in developing a non-toxic bacterial therapy, BacID, to deliver cancer-fighting drugs directly into tumors. This emerging technology holds promise for very safe and more effective treatment of cancers with high mortality rates, including liver, ovarian and metastatic breast cancer.

Clinical trials with participating cancer patients are estimated to begin in 2027. "This is exciting because we now have all the critical pieces for getting an effective bacterial treatment for cancer," says Neil Forbes, senior author of the research published recently in the journal Molecular Therapy and professor of chemical engineering at UMass Amherst.

"What we're trying to do is unlock the potential to treat late-stage cancers," adds lead author Vishnu Raman, who earned his Ph.D. in the Forbes Lab at the UMass Amherst Institute for Applied Life Sciences (IALS). "Bacteria naturally home to tumors, and because this treatment is so targeted, it can treat some cancers without the harsh side effects you'd see with other systematically delivered therapies, like chemotherapy."

The new findings are the culmination of more than a decade of research by Raman, chief scientific officer of Ernest Pharmaceuticals, an IALS startup co-founded by Raman, Forbes and co-author Nele Van Dessel, a bioengineer who developed the bacterial delivery system as a post-doctoral researcher in the Forbes Lab.

The team has been fine-tuning the development of non-toxic, genetically engineered strains of Salmonella to target tumors and then control the release of cancer-fighting drugs inside cancer cells. In addition to sparing healthy tissue from damage, this cancer treatment platform is able to deliver orders of magnitude more therapy than the administered dose because the simple-to-manufacture bacteria grow exponentially in tumors.

"We were focusing on how to make this strain really safe and user friendly," Raman says. "The genetic engineering steps we took made this strain at least 100 times safer than anything that's been tried in the past."

In this third-generation delivery strain, Raman figured out a way to control when the bacteria, after it has been intravenously injected, invades the cancer cells and delivers the therapy. This greatly improved the ability to target the tumors with higher concentrations of the drug therapy, while also making the treatment much safer.

"In the first-generation strain, we were basically relying on the bacteria's own brain to go find the tumor and deliver the therapy. But we couldn't control exactly when that was happening so there were risks associated with invading healthy cells, as well as pre-mature clearance of the bacteria before they colonize tumors, and we wanted to mitigate both risks," Raman says.

Early on in the research, the scientists discovered that it was the bacterial flagella—part of the cell that aids in movement—that enables the bacteria to invade cancer cells. So they engineered a genetic circuit in the bacteria that turns on the production of flagella with a simple, over-the-counter dose of aspirin. Without the turn-on switch provided by salicylic acid, the active metabolic product in the blood after a person takes an aspirin, the bacteria remain dormant in the tumor.

"One core part of this technology is the controlled activation of flagella," Raman explains. "And the other core part is once the bacteria go inside cancer cells, we engineered them with a suicide circuit. So they rupture on their own and deliver the therapy inside the cancer cell."

In pre-clinical research with mouse models, the bacteria is injected intravenously. "It goes everywhere, but then the immune system rapidly clears the attenuated bacteria from healthy organ tissue within two days. The bacteria continue to grow exponentially only within tumors during that time. On the third day, we give an over-the-counter dose of aspirin to trigger the bacteria to invade the cancer cells and then deliver the therapy," Raman says.

"We wanted to make it as simple as possible," he adds. "So the patient could get the infusion and three days later, at home, they just take an oral dose of aspirin."

The team is now focused on setting up the process to receive regulatory approval to begin clinical trials.

"We have seen a lot of growth in the area of microbial-based cancer treatment," Raman says, "and we are proud to be at the forefront of this field."

More information: Vishnu Raman et al, Controlling intracellular protein delivery, tumor colonization and tissue distribution using the master regulator flhDC in a clinically relevant ΔsseJ Salmonella strain, Molecular Therapy (2024). DOI: 10.1016/j.ymthe.2024.12.038

https://medicalxpress.com/news/2025-01-toxic-bacteria-high-mortality-cancers.html

Eliminating need to refrigerate vaccines and protein-based drugs

 A new storage technique can keep protein-based drugs and vaccines stable without keeping them cold. The discovery, led by researchers at Penn State, could eliminate the need for refrigeration for hundreds of life-saving medicines like insulin, monoclonal antibodies and viral vaccines.

"Over 80% of biologic drugs and 90% of vaccines require temperature-controlled conditions. This approach could revolutionize their storage and distribution, making them more accessible and affordable for everyone," said Scott Medina, study lead and William and Wendy Korb Early Career Professor of Biomedical Engineering at Penn State.

"This would save billions of dollars currently spent on keeping these products cold throughout the supply chain and potentially enable the use of protein therapies in environments where constant refrigeration is not possible."

The research was recently published in the journal Nature Communications. Through a series of experiments, the research team replaced the water-based solution commonly used in protein-based medications with a perfluorocarbon oil and tested five different proteins with a range of health-related functions such as antibodies and enzymes.

When tested in mice, the researchers found the new solution was just as effective as the refrigerated versions and showed no signs of toxicity, meaning there were no adverse health effects from the oil-based solution.

The researchers also found that the oil-based solution was naturally sterile for the protein samples, noting that they could not be contaminated by bacteria, fungi or viruses which require a water-based environment to grow and survive.

There was one problem: proteins in water-based environments spread themselves evenly throughout the liquid. In oil, they're not so soluble, Medina explained. So, the team developed a surfactant—a molecule that coats the surface of the protein—to shield the surface of the protein in a way that would allow it to evenly disperse itself throughout the solution.

The surfactant also created a protective shell around the protein, keeping it stable and preventing it from breaking down even at temperatures up to 212 degrees Fahrenheit, which would normally cause water to boil.

"Think of it like raincoats for proteins," said Medina, who is also affiliated with Penn State's Huck Institutes of the Life Sciences. "Just like a raincoat keeps you dry, this protective shell keeps the protein safe from heat and contamination, allowing it to stay stable and functional."

Protein-based drugs and vaccines are typically sensitive to heat, light and movement, all of which can cause them to lose their structure and function over time, Medina explained. Refrigeration helps to slow down that degradation process, so the medication will remain effective until it is administered.

"At high temperatures, proteins will start to unfold and become inactive," Medina said. "The unfolding happens because when the temperature increases, the energy of the water molecules will pull the protein apart and unfold it. Because of this, protein therapies often have to be stored in fridges or freezers to prevent the unfolding from happening."

Medina said these findings have the potential to limit or eliminate cold chain logistics, which is the supply network necessary for getting the therapies from where it is being produced to the various distribution centers prior to being administered to the patients.

In 2020, another team of researchers found that cold chain logistics are projected to cost $58 billion globally by 2026.

"If something goes wrong in the process, the activity of the protein therapy could be lost, the drug could no longer be effective or it becomes contaminated and the patients could potentially be harmed," Medina said.

The researchers said their approach has the potential to reduce costs and barriers for pharmaceutical companies, which could lead to more savings and better access for the patients in need of these therapies.

"This new method could also lower barriers and allow the drugs to be distributed in resource-scarce environments across all populations," Medina said. "We could even use this for those on the battlefield, where these therapies would be needed but access to refrigeration is limited."

In the future, the researchers aim to demonstrate that their method works with additional proteins and partner with pharmaceutical companies to stabilize protein molecules or peptides that could be used in a range of medications.

"We are currently in the process of securing patent rights and hope to partner with pharmaceutical companies to make their protein products more stable and accessible," Medina said.

The team includes Girish Kirimanjeswara, associate professor of veterinary and biomedical science; Atip Lawanprasert, Mariangely González Vargas and Arishya Dewan, Penn State graduate students; as well as Harminder Singh, postdoctoral scholar; and Sopida Pimcharoen, undergraduate student.

More information: Atip Lawanprasert et al, Heat stable and intrinsically sterile liquid protein formulations, Nature Communications (2024). DOI: 10.1038/s41467-024-55304-9

https://medicalxpress.com/news/2025-01-discovery-refrigerate-vaccines-protein-based.html

Multi-target approach counters tumor growth in several cancers

 The tissue adjacent to a tumor behaves differently than areas farther away. The tumor's cancerous cells influence their surroundings, blocking the body's immune defenses and creating a sort of haven in which the tumor can grow. Treatments that target some of these pro-tumor actions are effective in a number of cancers, but only for some patients; in others, these treatments have little effect.

Yale researchers have developed a new approach that simultaneously targets several of these pro-tumor actions at once, which they have demonstrated can effectively reduce tumor growth across several types of cancers.

Their new findings, published in Nature Biotechnology, point to a potential new treatment that may benefit more patients than current therapeutic options.

"Traditional therapies target one molecule in the tumor microenvironment, but the microenvironment is so complex, targeting one thing doesn't always work," said Sidi Chen, an associate professor of genetics and neurosurgery at Yale School of Medicine and senior author of the study. "For example, the most well-known of these immunotherapies only benefits 20 to 30% of patients."

When these therapies don't work, it can be because the molecule they're targeting doesn't play a major role in the individual's tumor or because there is some other molecule that has a similar effect and compensates for the loss of the one targeted by the treatment.

"Or it can be even more complex with say a large network of pathways within the tumor microenvironment all working to suppress the body's immune response," said Chen, who is also a researcher with the Systems Biology Institute at Yale's West Campus. "So how do you hit multiple targets in the same go?"

For their approach, Chen and his colleagues used a gene editing molecule called Cas13, which targets and degrades RNA. (Its more widely discussed counterpart, known as Cas9, targets DNA.) One benefit of Cas13 is its ability to target multiple genes with one molecular package. The researchers identified several genes that can suppress immune responses and developed a Cas13 system that targeted each of them.

When they delivered the Cas13 package into tumor microenvironments in mice, they found that it silenced those immune suppression genes (essentially un-silencing or re-activating the immune system), remodeled the microenvironment, and boosted antitumor immune responses. The result was reduced tumor growth across four types of cancers: breast cancer, melanoma, pancreatic cancer, and colon cancer.

While more research will be required to further optimize this approach for efficacy and safety, researchers say this technology holds promise as both an "off-the-shelf" treatment for more general use and one that can be tailored for specific individuals by swapping gene targets as necessary.

The researchers are continuing this line of research with the goal of working toward translation and clinical trials.

Co-authors Feifei Zhang, Guangchuan Wang, and Ryan Chow, all of Yale, led the research with Chen.

More information: Feifei Zhang et al, Multiplexed inhibition of immunosuppressive genes with Cas13d for combinatorial cancer immunotherapy, Nature Biotechnology (2025). DOI: 10.1038/s41587-024-02535-2

https://medicalxpress.com/news/2025-01-multi-approach-counters-tumor-growth.html

'Study shows teletherapy has not improved access to mental health care for those who cannot pay'

 A small team of psychiatrists at Columbia University, in the U.S., has found that despite an increase in the use of teletherapy over the past several years by both psychotherapists and their patients, access to such care has not increased for those who cannot afford to pay for it.

In their study, published in the American Journal of Psychiatry, the group used data from prior research efforts to show that the use of technology to reach patients in need of psychotherapy has not led to an increase in use by low-income people.

Over the past several years, the use of technology like Zoom has become more popular among therapists. Teletherapy frees both the therapist and the patient from having to travel to a site for sessions. When the pandemic hit, these services grew much more popular.

As the researchers note, prior to the pandemic, the percentage of Americans receiving psychotherapy ranged from between 3% and 4%. During the pandemic, the percentage rose to approximately 8.5% and has remained at higher levels since then, primarily due to the ease of access online.

In this new effort, the research team revisited the data from a prior research effort focused on highlighting trends in patients seeking outpatient care in the U.S.—a study involving 89,619 psychotherapy patients. The researchers found that despite the hope that increasing the use of teletherapy would lead to more help for low-income people, there was no noticeable improvement. Patients using such services tended to be young, well educated and in higher income brackets.

The researchers also looked at data from another study focused on the use of telehealth by children and adolescents and found similar results. Most were members of high-income families, especially those with good health insurance.

The research team suggests that teletherapy has done little to improve access to mental health care for low-income people, primarily because those who offer such services expect to be paid the same as for in-office sessions, either by clients or their insurance companies.

More information: Mark Olfson et al, Use of Telemental Health Care by Children and Adolescents in the United States, American Journal of Psychiatry (2025). DOI: 10.1176/appi.ajp.20240193

https://medicalxpress.com/news/2025-01-teletherapy-access-mental-health-pay.html

Giuliani to keep his home in settlement with election workers

 Rudy Giuliani reached a deal Thursday that lets the cash-strapped ex-New York City mayor keep his homes and belongings, including prized World Series rings, in exchange for unspecified compensation and a promise to never again speak ill of two former Georgia elections workers who won a $148 million defamation judgment against him.

The agreement resolves all pending litigation between Giuliani and the former election workers, Ruby Freeman and her daughter, Wandrea “Shaye” Moss. It also led to the cancellation of a trial that was supposed to begin Thursday to decide the ownership of his Florida condominium and three World Series rings that Giuliani, a prominent New York Yankees fan, had received from the team.

Giuliani, 80, was supposed to be the trial’s first witness, but he never showed up to the federal courthouse in Manhattan.

Left unanswered: How much Giuliani agreed to pay the women, how he’s footing the bill and whether anyone is helping him.

Giuliani had already begun turning over assets prior to the settlement, including his Manhattan apartment, which is worth about $5 million, a 1980 Mercedes once owned by movie star Lauren Bacall, numerous luxury watches and other belongings. His total assets are worth about $10 million.

Freeman and Moss won the massive judgment after saying Giuliani’s lies about them following President-elect Donald Trump’s 2020 election loss led to death threats.

“The past four years have been a living nightmare. We have fought to clear our names, restore our reputations, and prove that we did nothing wrong,” the women said in a statement. “Today is a major milestone in our journey.”

With the agreement, they said, “we can now move forward with our lives.”

Giuliani said in a statement posted on social media and read to reporters by his lawyer that the settlement satisfies the judgment against him but “does not involve an admission of liability or wrongdoing.”

“I am satisfied with and have no grievances relating to the result we have reached,” Giuliani said, adding that it allowed him to retain his Manhattan apartment and Florida condominium, as well as all of his personal belongings.

“No one deserves to be subjected to threats, harassment, or intimidation,” the former mayor wrote. “This litigation has taken its toll on all parties. This whole episode was unfortunate. I and the Plaintiffs have agreed not to ever talk about each other in any defamatory manner, and I urge others to do the same.”

Giuliani’s lawyer, Joseph Cammarata, said the deal sprung from negotiations over the last three days that went “into the wee hours of the night.”

Had an agreement not been reached, Giuliani would have been in court Thursday testifying before the same judge who last week found him in contempt for failing to turn over information on some of his assets to the women’s lawyers. As punishment, Judge Lewis J. Liman banned Giuliani from using certain evidence.

The trial, now averted, was not intended to relitigate whether Giuliani defamed the women or the size of the judgment against him.

Rather, it was to decide the fate of some of his prized assets, including his Florida condo, which is believed to be worth more than $3 million, and the World Series rings, which he touted as mementos of his time as “New York’s No. 1 Yankee fan.”

Giuliani argued that he established residence near Trump in Palm Beach, Florida, a year ago, but lawyers for Freeman and Moss say he continued to operate as if his New York apartment was his residence until he surrendered it last fall as part of the process of satisfying the judgment. Giuliani said he gave the rings to his son in 2018.

Andrew Giuliani said it’s his understanding that he’ll keep the rings.

Giuliani was also found in contempt last week in Washington, D.C. The judge there found that he continued to slander the election workers by repeating false claims that they counted votes corruptly during the 2020 presidential contest.

Giuliani, once heralded as “America’s Mayor” for his post-9/11 leadership, served for a time as Trump’s personal attorney during the president-elect’s first term.

“SAVE RUDY!!!” Trump posted Sunday on his Truth Social platform.

As the lawyers were finalizing the settlement, Giuliani posted a video on social media showing a dog named Vinny on the grounds of Trump’s Florida estate. The dog, the post said, “loves hanging out at Mar-a-Lago” but is “ready to spend a lot more time in Washington, D.C.,” supporting Trump. It wasn’t clear when the recording was made.

Giuliani filed for bankruptcy within days of the defamation verdict, pausing collection. After a judge threw out the case last July, finding that the former mayor had thumbed his nose at the process, Freeman and Moss sued to enforce payment.

As of last May, Giuliani had just over $1 million in a retirement account, nearly $94,000 in personal cash and about $237,000 in his company’s account, according to court filings.

At a recent hearing, Giuliani said he was “not impoverished” but that he didn’t have access to most of his remaining assets.

“Everything I have is tied up,” he lamented.

Giuliani said in sworn deposition testimony last month that after leaving office in 2002, the late Yankees owner George Steinbrenner gave him rings commemorating each of the four World Series the team won while he was mayor.

Giuliani testified that he insisted on paying for the rings, which were the same as the ones the players received, and told Steinbrenner: “These are for Andrew.” He said he immediately gave one to Andrew, a teen at the time, and kept three others for safekeeping. He estimated their total worth at $27,000.

https://apnews.com/article/giuliani-georgia-election-defamation-24a5b799fc7edadab9a82020c55c2bfb

North Korea denounces US for sending aircraft over Korean peninsula, KCNA reports

 North Korea denounced the United States for sending military aircraft over the Korean peninsula several times this month, as well as the U.S., Japan and South Korea for holding an air military exercise, state media KCNA reported on Friday.

North Korea also denounced the joint Nuclear Consultative Group (NCG) between the U.S. and South Korea that seeks to manage North Korea's nuclear threat, the report said.

North Korea denounced the United States for sending military aircraft over the Korean peninsula several times this month, as well as the U.S., Japan and South Korea for holding an air military exercise, state media KCNA reported on Friday.

North Korea also denounced the joint Nuclear Consultative Group (NCG) between the U.S. and South Korea that seeks to manage North Korea's nuclear threat, the report said.

https://www.usnews.com/news/world/articles/2025-01-16/north-korea-denounces-us-for-sending-aircraft-over-korean-peninsula-kcna-reports

General Motors Reaches Settlement With FTC for Selling Consumer Data

 General Motors reached an agreement to settle allegations that the automaker shared drivers' locations and behavior data without their consent, the Federal Trade Commission said on Thursday.

The Detroit company failed to clearly disclose to consumers that it collected precise geolocation and driving behavior data through its OnStar connected vehicle service and OnStar Smart Driver feature, the FTC alleged. This data was then sold to third parties, including consumer reporting agencies, without consumers' permission.

GM didn't immediately respond to a request for comment.

Under the settlement GM will be banned from disclosing consumers' geolocation and driver behavior data to consumer reporting agencies for five years. The company will take additional steps to provide greater transparency and choice to consumers over the collection, use and disclosure of their connected vehicle data, the agency said.

The FTC alleged that GM customers were encouraged to sign up for OnStar on the basis that it would be used to help them assess their driving habits. The company, however, failed to clearly disclose the types of information the service collected, or that the information would be sold.

Additionally, GM's enrollment process for this feature was confusing and misleading, the agency said, noting that some consumers were unaware that they had signed up for the service.

https://www.morningstar.com/news/dow-jones/202501169655/general-motors-reaches-settlement-with-ftc-for-selling-consumer-data