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Dubbed “living drugs,” CAR T cells are bioengineered from a patient’s own immune cells to make them better able to hunt and destroy cancer.

The treatment is successfully tackling previously untreatable blood cancers. Six therapies are already approved by the FDA. Over a thousand clinical trials are underway. These aren’t limited to cancer—they cover a range of difficult medical problems such as autoimmune diseases, heart conditions, and viral infections including HIV. They may even slow down the biological processes that contribute to aging.

But CAR T has an Achilles heel.

Once injected into the body, the cells often slowly dwindle. Called “exhaustion,” this process erodes therapeutic effect over time and has dire medical consequences. According to Dr. Evan Weber at the University of Pennsylvania, more than 50 percent of people who respond to CAR T therapies eventually relapse. This may also be why CAR T cells have struggled to fight off solid tumors in breast, pancreatic, or deadly brain cancers.

This month, two teams found a potential solution—make CAR T cells more like stem cells. Known for their regenerative abilities, stem cells easily repopulate the body. Both teams identified the same protein “master switch” to make engineered cells resemble stem cells.

One study, led by Weber, found that adding the protein, called FOXO1, revved up metabolism and health in CAR T cells in mice. Another study from a team at the Peter MacCallum Cancer Center in Australia found FOXO1-boosted cells appeared genetically similar to immune stem cells and were better able to fend off solid tumors.

While still early, “these findings may help improve the design of CAR T cell therapies and potentially benefit a wider range of patients,” said Weber in a press release.

I Remember

Here’s how CAR T cell therapy usually works.

The approach focuses on T cells, a particular type of immune cell that naturally hunts downs and eliminates infections and cancers inside the body. Enemy cells are dotted with a specific set of proteins, a kind of cellular fingerprint, that T cells recognize and latch onto.

Tumors also have a unique signature. But they can be sneaky, with some eventually developing ways to evade immune surveillance. In solid cancers, for example, they can pump out chemicals that fight off immune cell defenders, allowing the cancer to grow and spread.

CAR T cells are designed to override these barriers.

To make them, medical practitioners remove T cells from the body and genetically engineer them to produce tailormade protein hooks targeting a particular protein on tumor cells. The supercharged T cells are then grown in petri dishes and transfused back into the body.

In the beginning, CAR T was a last-resort blood cancer treatment, but now it’s a first-line therapy. Keeping the engineered cells around inside the body, however, has been a struggle. With time, the cells stop dividing and become dysfunctional, potentially allowing the cancer to relapse.

The Translator

To tackle cell exhaustion, Weber’s team found inspiration in the body itself.

Our immune system has a cellular ledger tracking previous infections. The cells making up this ledger are called memory T cells. They’re a formidable military reserve, a portion of which resemble stem cells. When the immune system detects an invader it’s seen before—a virus, bacteria, or cancer cell—these reserve cells rapidly proliferate to fend off the attack.

CAR T cells don’t usually have this ability. Inside multiple cancers, they eventually die off—allowing cancers to return. Why?

In 2012, Dr. Crystal Mackall at Stanford University found several changes in gene expression that lead to CAR T cell exhaustion. In the new study, together with Weber, the team discovered a protein, FOXO1, that could lengthen CAR T’s effects.

In one test, a drug that inhibited FOXO1 caused CAR T cells to rapidly fail and eventually die in petri dishes. Erasing genes encoding FOXO1 also hindered the cells and increased signs of CAR T exhaustion. When infused into mice with leukemia, CAR T cells without FOXO1 couldn’t treat the cancer. By contrast, increasing levels of FOXO1 helped the cells readily fight it off.

Analyzing genes related to FOXO1, the team found they were mostly connected to immune cell memory. It’s likely that adding the gene encoding FOXO1 to CAR T cells promotes a stable memory for the cells, so they can easily recognize potential harm—be it cancer or pathogen—long after the initial infection.

When treating mice with leukemia, a single dose of the FOXO1-enhanced cells decreased cancer growth and increased survival up to five-fold compared to standard CAR T therapy. The enhanced treatment also tackled a type of bone cancer in mice, which is often hard to treat without surgery and chemotherapy.

An Immune Link

Meanwhile, the Australian team also zeroed in on FOXO1. Led by Drs. Junyun Lai, Paul Beavis, and Phillip Darcy, the team was looking for protein candidates to enhance CAR T longevity.

The idea was, like their natural counterparts, engineered CAR T cells also need a healthy metabolism to thrive and divide.

They started by analyzing a protein previously shown to enhance CAR T metabolism, potentially lowering the chances of exhaustion. Mapping the epigenome and transcriptome in CAR T cells—both of which tell us how genes are expressed—they also discovered FOXO1 regulating CAR T cell longevity.

As a proof of concept, the team induced exhaustion in the engineered cells by increasingly restricting their ability to divide.

In mice with cancer, cells supercharged with FOXO1 lasted longer by months than those that hadn’t been boosted. The critters’ liver and kidney functions remained normal, and they didn’t lose weight during the treatment, a marker of overall health. The FOXO1 boost also changed how genes were expressed in the cells—they looked younger, as if in a stem cell-like state.

The new recipe also worked in T cells donated by six people with cancer who had undergone standard CAR T therapy. Adding a dose of FOXO1 to these cells increased their metabolism.

Multiple CAR T clinical trials are ongoing. But “the effects of such cells are transient and do not provide long-term protection against exhaustion,” wrote Darcy and team. In other words, durability is key for CAR T cells to live up to their full potential.

A FOXO1 boost offers a way—although it may not be the only way.

“By studying factors that drive memory in T cells, like FOXO1, we can enhance our understanding of why CAR T cells persist and work more effectively in some patients compared to others,” said Weber.

Image Credit: Gerardo Sotillo, Stanford Medicine

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While politicians who should know better waste time worrying about green bubbles, Apple continues to explore opportunities in global markets as its traditional ones become increasingly stagnant. 

Apple is also seeking ways to become less exposed to America’s growing politically driven tension against China, a nation that has been a strong partner for Cupertino — and therefore, also for US soft power’s success.

Following his visit to China in March, Apple CEO Tim Cook spent a week in Indonesia, Vietnam, and Singapore. The week was no idle executive jolly, nor should it be seen as an opportunity to purchase some new carbon offsets to justify use of the executive jet. Apple’s boss was there to do business — with a few splendid social media moments to add a little extra shine. 

Preparing the ground in Vietnam

During a two-day visit to Vietnam, Cook announced plans to increase spending on manufacturing suppliers there. Luxshare, Foxconn, Compal, and GoerTek already employ 150,000 people in Vietnam, while Apple and third parties support another 50,000 jobs. “From cooperating with local suppliers, to supporting clean water projects and educational opportunities, we are committed to continuing to strengthen connections in Vietnam,” Cook said in a statement.

The current thinking is that Apple sees Vietnam as a hub for Mac, AirPod production.

Nurturing talent in Indonesia

Cook’s tour then stopped in Indonesia, where Apple’s leader met President Joko Widodo to discuss potential investments. Cook even spoke at a news conference, during which he confirmed discussions about manufacturing and characterized the investment opportunity there as “endless.”

Apple doesn’t really have a strong manufacturing connection with Indonesia, but is making significant investments in people there. During Cook’s visit, the company announced its fourth developer academy in Bali. “We’ve seen many times over that a line of code can change the world — and in Indonesia, we’re investing in the creativity and skills of people determined to prove it,” Cook said in a statement. 

Expanding corporate staff in Singapore

Finally, Cook stopped in Singapore, where he visited Apple stores and the company’s new Developer Center. Apple had big news here too, announcing a $250 million investment to extend its existing campus in Ang Mo Kio. That campus is believed to act as a regional hub for corporate operations across the region. Apple first opened up in Singapore in 1981 when it was making the Apple II systems.

Feet on the ground

Apple’s connection with the region is nothing new. It has worked with suppliers and manufacturers across the Asia-Pacific region for years and Cook led those teams. While he was Apple’s Chief Operating Office, he was the leading architect of the company’s globalized, highly efficient supply chain. (He might have engaged in similar negotiations before Apple, when he led procurement at Compaq.)

Staying in the arena

Today, as Apple battles stormy regulatory seas, Cook seems to be leaning deep into his experience to guide the company through. That means meeting national leaders at the highest level in countries in which he sees signs of future opportunity. It builds on Cook’s track record — Apple’s work in India means that nation is accelerating to become a top three market for the company, and the company’s investments across the region should help it build its presence across adjacent national economies.

After all, as Cook once said, “The sidelines are not where you want to live your life. The world needs you in the arena,” and keeping that place in that arena is precisely what Apple needs to do. It’s also important to note that it’s about this time of year the company finalizes production deals with suppliers across the region.

Given the strategic importance of those arrangements, particularly during such interesting times, who better to sign the final commitment than the CEO? After all, we know new iPhones, Macs, iPads, and Vision family products are coming. They just won’t necessarily be made in China.

Please follow me on Mastodon, or join me in the AppleHolic’s bar & grill and Apple Discussions groups on MeWe.

Apple, Manufacturing Industry, Vendors and Providers

E-maily poslané ze schránek @outlook.cz do Gmailu nedorazí •Google doménu považuje za nedůvěryhodnou •Microsoft přetrvávající situaci řeší a nabízí dočasné řešení

Still available in Hong Kong and Macau, for now

Apple has removed four apps from its China-regional app store, including Meta's WhatsApp and Threads, after it was ordered to do so by Beijing for security reasons.…

Technology, research, and government sectors in the Asia-Pacific region have been targeted by a threat actor called BlackTech as part of a recent cyber attack wave. The intrusions pave the way for an updated version of modular backdoor dubbed Waterbear as well as its enhanced successor referred to as Deuterbear. "Waterbear is known for its complexity, as it

Technology, research, and government sectors in the Asia-Pacific region have been targeted by a threat actor called BlackTech as part of a recent cyber attack wave. The intrusions pave the way for an updated version of modular backdoor dubbed Waterbear as well as its enhanced successor referred to as Deuterbear. "Waterbear is known for its complexity, as it Newsroomhttp://www.blogger.com/profile/[email protected]

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Microsoft is reminding customers that support for its Office 2016 and Office 2019 suites and related productivity servers will end on Oct. 14, 2025. 

Microsoft issued the reminder this week that applications in the two Office suites — including versions of Excel, Outlook, PowerPoint, Word, and others — will no longer receive security fixes, bug fixes, and technical updates after the support date passes. 

That’s also true for Exchange Server 2016 and 2019, as well as Skype for Business Server 2015 and 2019, Microsoft said in a blog post Monday (Oct. 14, 2025 also happens to be the same date for Windows 10 support to end.)

Using these products after the end of support  leaves  business users vulnerable to “potential security threats, productivity losses, and compliance issues,” said Mariana Prudencio, senior product marketing manager at Microsoft. 

Not surprisingly, the company is pushing customers to cloud-based options. Microsoft recommends customers update to cloud-hosted versions of the software such as Microsoft 365 E3. Another option for Office 2016 and 2019 users is the Office Long-Term Servicing Channel, Microsoft said, which extends support into 2026.

Those that want to continue running Exchange Server on-premises are advised to prepare to migrate to the upcoming Exchange Server slated to arrive in 2025 prior to the end of support date. Microsoft recommends customers move to Exchange Server 2019 to ease this transition.

Businesses should be particularly wary of the looming end of support for Exchange servers, said Jack Gold, founder and principal analyst at J. Gold Associates. 

A lack of security updates would expose them to “a lot of risk,” he said, “since a large portion of threats are targeted against email and email servers, and stolen identities pose a big risk here.” Businesses that continue to run Exchange on-prem tend to be smaller, so it might be more difficult or costly for them to migrate, said Gold. 

“The larger companies have mostly migrated to online already,” he said.

End of support for the Office suites, on the other hand, is less problematic, said Gold, particularly for small business users. While security updates are important, smaller firms tend to run third-party antivirus and other security tools that can mitigate many potential threats. 

Some smaller business will look to migrate to Microsoft’s cloud-based Office apps, but many will opt to remain on the outdated versions past the support date and update the software in line with upgrades of other equipment. 

“And it is still possible to buy a standalone Office suite if you’re not in need of back-end servers, as many smaller businesses don’t require, so you can update that way,” said Gold. 

Microsoft, Microsoft Office, Office Suites

Aimed at accelerating progress in AI development and responsible AI deployment, Alphabet-owned Google is consolidating its teams that are responsible for building AI models across Google Research and Google DeepMind, its CEO Sundar Pichai said Thursday in a note to its employees.  All AI “work will now sit in Google DeepMind,” Pichai specified in the note.

This restructuring will “scale our capacity to deliver capable AI for our users, partners and customers,” Pichai said in the note. “This will simplify development by concentrating compute-intensive model building in one place and establishing single access points for PAs looking to take these models and build generative AI applications.”

The Google DeepMind team will be led by Demis Hassabis, said the note.

Google formed Google DeepMind exactly a year ago by combining two research teams in the AI field – the Brain Team of Google Research, and DeepMind. This focused team, backed by the computational prowess of Google “will significantly accelerate our progress in AI,” Pichai had said in an April 2023 note. Gemini models were created by Google DeepMind.

Google Research is the research arm of Google, dedicated to AI and computer science to develop next-generation technologies that benefit Google products having key focus areas including AI/ML, Responsible Human-centric Technology, Science & Societal Impact, Computing Paradigms, and Algorithms and Optimization.

What’s new, now?

Google is now consolidating all its AI units one to “simplify our structure and improve velocity and execution – such as bringing together the Brain team in Google Research with teams in DeepMind, which helped accelerate our Gemini models; unifying our ML infrastructure and ML developer teams to enable faster decisions, smarter compute allocation, and a better customer experience; and bringing our Search teams under one leader,” the note added.

The move, Pichai said, also gives Google Research a clear mandate to continue investing in three key areas that align with Google’s mission — computing systems, foundational ML and algorithms, and applied science and society.

“Consolidating all of Google’s AI teams, including Google Research and DeepMind, into one unit under Google DeepMind likely reflects a strategic move aimed at streamlining and optimizing AI development and deployment across the company,” said Pradeepta Mishra, an AI expert and co-founder of cybersecurity firm Data Safeguard.

Besides, Google is reaffirming its commitment to responsible AI deployment by ramping up its Responsible AI Team’s roles and accountability. Teams focusing on Responsible AI within the Google Research team will now move to Google DeepMind to be closer to ‘where the models are built and scaled’, said the note.

Similarly, “other responsibility teams” are moving into our central “Trust and Safety” team where the company is investing more in “AI testing and evaluations” to enhance product accuracy and responsiveness. “These shifts create clearer responsibility and accountability at every level as we build and deploy, and strengthen the feedback loop between models, products, and users,” Pichai added in the note.

Recognizing the potential of AI, Google is also formalizing collaboration between its AI divisions, software, and computing platforms. “So we are formalizing the collaboration between DSPA and P&E and bringing the teams together in a new PA called Platforms & Devices.”

Having a unified team across Platforms & Devices will help Google deliver higher-quality products and experiences for its users and partners, Pichai said. It will help us turbocharge the Android and Chrome ecosystems, and bring the best innovations to partners faster — as we did with Circle to Search with Samsung. And internally, it will also speed up decision-making.”

How it helps Google

Merging teams eliminates redundancy and fosters closer collaboration between researchers and developers. This could accelerate the development cycle for new AI products and features. All these moves, Pichai said in the note, “will help us work with greater focus and clarity towards our mission.”

“With one central unit, decision-making around resource allocation and project priorities becomes more efficient,” Mishra added. The AI landscape is fiercely competitive. Data Safeguard’s Mishra said this consolidation could help Google “stay ahead of the curve by accelerating innovation.”

“By integrating research and development under one roof, Google might create more unified and impactful AI products across its platforms (Search, Assistant, etc.). Streamlined operations could lead to better resource utilization and potentially cost savings,” said Mishra.

Google

It’s the second time the World-Check list has fallen into the wrong hands

The World-Check database used by businesses to verify the trustworthiness of users has fallen into the hands of cybercriminals.…

Attackers are increasingly making use of “networkless” attack techniques targeting cloud apps and identities. Here’s how attackers can (and are) compromising organizations – without ever needing to touch the endpoint or conventional networked systems and services.  Before getting into the details of the attack techniques being used, let’s discuss why

Attackers are increasingly making use of “networkless” attack techniques targeting cloud apps and identities. Here’s how attackers can (and are) compromising organizations – without ever needing to touch the endpoint or conventional networked systems and services.  Before getting into the details of the attack techniques being used, let’s discuss why The Hacker Newshttp://www.blogger.com/profile/[email protected]