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Saturday, October 3, 2026

'Siberian Plague-Lab Death Draws FSB Security Escort For Ambulances'

A possible plague case in Siberia has triggered a major containment effort after the death of a 28-year-old employee of an anti-plague laboratory. A hospital wing is under quarantine, nearly 200 people are reportedly under observation, and Russia's chief sanitary official has flown in. Local outlets say FSB units have been escorting ambulances carrying the woman's contacts for examination.

The authorities are clearly taking the threat seriously - but getting a straight answer out of the feds is another matter. Irkutsk Governor Igor Kobzev is still calling it a "particularly dangerous infection," while assuring residents that every identified contact is symptom-free and testing negative.

The dead lab worker has been identified as Daria Shipilova, a laboratory assistant at the Irkutsk Anti-Plague Research Institute of Siberia and the Far East, according to Lyudi Baikala and REN TV. She was admitted to hospital in Shelekhov with severe pneumonia, placed on a ventilator, and died. Reports differ slightly on the timeline: The Moscow Times gives a September 29 admission and a Thursday death (48 hours), while Lyudi Baikala says she spent three days in hospital.

According to The Moscow Times, Shipilova told medical staff she had accidentally broken a tube containing live bacteria while collecting samples. Lyudi Baikala, citing journalist Pavel Stepanov and the Telegram channel Mash, placed the alleged accident on September 25 and linked it to plague bacteria. Those reports describe the illness as pneumonic plague, although neither that diagnosis nor the laboratory accident has been publicly confirmed by investigators. IRK.ru reported that doctors initially suspected severe COVID and sent her to the hospital's COVID center.

By the evening of October 1, security and administrative officials were meeting in Irkutsk. Lyudi Baikala, citing a source close to law enforcement, reported that FSB units began accompanying ambulances transporting Shipilova's contacts for examination that day. The Insider carried the same account, while residents reported seeing people in protective suits on the streets. The FSB has not confirmed the escorts.

Shelekhov district head Maxim Modin confirmed that the hospital's inpatient department was under quarantine; the outpatient clinic remained open. Kobzev said the sanitary-epidemiological commission had convened on October 2 over a suspected "particularly dangerous infection." Anna Popova, who heads Rospotrebnadzor, the federal agency that runs Russia's disease surveillance and owns the anti-plague institutes, traveled to attend. The governor told TASS it was premature to identify the disease and made no mention of a death. Irkutsk also postponed a city cleanup day scheduled for October 3.

The reported contact numbers suggest how widely authorities are casting the net. REN TV and Izvestia put the total at roughly 197, with 189 hospitalized for observation: 114 in one facility, 63 in another, and 12 at the anti-plague institute. Eight remained outside hospital, and some accounts said the list was still growing. No secondary infection has been confirmed. Kobzev's October 2 statement said the contacts had no symptoms and negative tests, although some media reports claimed several people under observation had developed symptoms.

First Official Use Of 'Plague'

The leader of Buryatia (the next region over from the lab), Alexey Tsydenov, wrote that the woman who died of plague in Irkutsk region had not visited his republic. Citing Rospotrebnadzor and his government, he also said Buryatia had no plague foci, including along the Mongolian border. But even that acknowledgment became less definite: Meduza reported that he later edited the post to say she "may have died of plague." He did not identify the pneumonic form.

Meanwhile, competing accounts sent Shipilova to Thailand or Buryatia before she fell ill. Tsydenov denied the Buryatia visit. Gennady Onishchenko, who ran Rospotrebnadzor until 2013, questioned whether plague was involved at all, pointing to dormant rodents and fleas and snow already falling in Buryatia. That argument addresses a possible wildlife exposure; it does not resolve the allegation that she broke a tube of bacteria at work.

Izvestia and the Telegram channel Ostorozhno Novosti both report that investigators have opened a criminal case under Article 236, which covers sanitary violations that cause death by negligence. Nobody has confirmed it on the record. That charge only makes sense if somebody broke a rule at work.

By Saturday, some of the public information was disappearing. Baikalsk's administration posted a notice urging residents to limit travel to Shelekhov and nearby settlements, citing "unofficial information" about a plague case. Roughly two hours later, the notice was gone. REN TV also deleted five Telegram posts about the Shelekhov hospitalization figures.

Kobzev's Saturday post concerned an inspection by Roszdravnadzor, the healthcare-quality regulator rather than the epidemiological service, and did not address the infection. Comments asking why there was still no official statement went unanswered. Meanwhile, Lyudi Baikala reported that pharmacies in Irkutsk and Shelekhov had sold out of antibiotics.

The institute where Shipilova worked was founded in 1934 to fight plague and still leads plague surveillance for the region, alongside cholera, anthrax and tularemia. It is one of five such institutes nationally and the only one covering Siberia and the Far East. Natural plague foci remain in parts of southern Siberia, including Tuva, Altai and Transbaikal. Russia's last widely reported human case involved a child in the Altai Republic in 2016 and was linked to marmots.

The negative tests are welcome news, and the reports so far do not establish a spreading outbreak. But a young laboratory worker is dead, a hospital wing is quarantined, and almost 200 contacts have reportedly been identified. "Particularly dangerous infection" is a description of the stakes. It still isn't an explanation of what happened.

https://www.zerohedge.com/medical/siberian-plague-lab-death-draws-fsb-escort-ambulances

'UAE to release Iranian prisoners, Iranian state media says'

A number of Iranian prisoners held in the United Arab Emirates will be released and returned to Iran, Iranian state media reported Saturday.

The report said the releases followed efforts by an Iranian diplomatic and security delegation.

It did not say how many prisoners would be freed, identify them or provide details about why they had been detained.

https://www.iranintl.com/en/202610033365

Saudi-led coalition said to strike Yemen's capital

The Saudi Arabian-led coalition has targeted Yemen's capital, Sanaa, the Houthi-affiliated Saba News Agency reported.

The outlet also alleged that the coalition launched missile strikes on the Sahar district in the northwestern Sa'dah Governorate. The district has often been cited as Yemen's food basket.

Previously, in response to Saudi Arabia's recent attacks, the Houthis claimed they targeted Saudi Aramco facilities in Riyadh.

https://breakingthenews.net/Article/Saudi-led-coalition-said-to-strike-Yemen's-capital/67228514

Iran’s terrifying new terror tactic may be turning airline pilots into 9/11-style attackers: former IDF colonel

The hijacking of the Dubai airliner carrying Israeli passengers might be the beginning of a horrifying new terrorist tactic of recruiting and radicalizing real pilots to do 9/11-style attacks, a former IDF colonel and veteran intelligence officer warns.

“An individual doesn’t get the idea on his own to crash a plane full of people including himself. Somebody told him that if you do that you get your 72 virgins,” Miri Eisin, now an Israeli government spokesman, told The Post.

“If you think back to past plane hijackings, including 9/11, the hijacker was never the pilot of the plane. . . . This could be a new kind of suicide bomber,” she said.

Eisin, who served in the Israel Defense Forces as an intelligence officer for over 20 years, said she immediately suspected Iran’s hand in the near-tragic FlyDubai hijacking — though she was careful to stress she has no direct evidence and that the investigation is ongoing.

President Trump has also suggested Iran might have been involved, but did not elaborate.

The pilot has been identified by The Wall Street Journal as an Omani national named Hamam al-Hammami. He had previously been banned from flying by Oman due to suspicions he had become radicalized, according to the publication.

Israeli Prime Minister Benjamin Netanyahu said that the attacker had been subject to “Islamic radicalization.”

“This to me is very much something that could have come from Hezbollah or the IRGC Quds Force, this is the kind of things that they think of,” she said.

Eisin said that Iran, if responsible for the attack, may be trying to unleash a new kind of suicide bomber by infiltrating airlines with radicalized pilots who could launch an attack at any time.

Eisin said a pilot’s professional training would not make him immune to extremist indoctrination.

“Just because someone’s a pilot doesn’t mean they can’t be radicalized, people from all walks of life could be radicalized. [Syrian dictator] Bashar al-Assad was a doctor, Josef Mengele was a doctor,” she said.

“And if you kill Israelis, the whole world applauds you,” she added.

Oded Ailam, a former deputy head of global operations for Israel’s Mossad intelligence agency, said recruiting a commercial pilot to deliberately crash a plane would require a far more elaborate process than persuading a young suicide bomber to carry out an attack.

“Recruiting and convincing a pilot to do something like that, it’s not the same as telling a 15-year-old to strap on a bomb and walk into a promenade and explode himself. This is a very sophisticated and long operation,” he said.

Ailam, who is now a researcher at the Jerusalem Center for Security and Foreign Affairs, said that it’s likely that Iran was able to radicalize the pilot passively without formally recruiting him via its vast array of anti-Israel propaganda online and in other venues.

Ailam said that the prospect of lone wolf extremists could pose an even more dangerous threat to air travel than organized terror cells that could be identified and disrupted.

“Terror combined with mental disturbances in the pilot, when you combine it together the outcome is horrific. There are a lot of people who are being radicalized who are airline pilots,” he said.

Ailam said the flydubai attack will likely lead governments to rethink their post-9/11 security measures, and he predicts airlines will soon have to install technology that lets crew access the cockpit in the case of a copycat attack.

“It’s impossible to screen every pilot, the answer will have to be technological,” he said.

https://nypost.com/2026/10/03/world-news/irans-terrifying-new-terror-tactic-may-be-turning-airline-pilots-into-9-11-style-attackers-former-idf-colonel-warns/

Madrid housing protests fuel speculation over Spanish election

Thousands of people took to the streets of Madrid on Saturday, joining nationwide protests over housing costs that could increase pressure on Prime Minister Pedro Sánchez to call a snap election.

The demonstrations were sparked by last week’s eviction of an 87-year-old disabled woman, underlining that housing is top concern for many Spaniards. On Friday, parliament rejected the government’s emergency housing package, which could prompt Sanchez to bring forward elections due for next year.

The protesters, which set off from different parts of the Spanish capital, headed toward Plaza de Cibeles, a landmark square and traffic junction in central Madrid. The demonstration was organized by the Tenants’ Union, who also called for marches across more than 50 cities throughout the weekend.

The protesters in Madrid chanted: “What’s going on? We don’t have a home!” and, at intervals, raised their arms and shook their house keys, producing a ripple of metallic jangle through the crowd. Signs called for a general strike and rent controls.

“I rent, and if I want to move, which I’d like to do, I can’t, because prices are exorbitant,” said Nuria López, a senior compliance officer at a large company, who said 40% of her wages go on rent. “And if I want to buy a home, I can’t do that either, because I don’t have the money for a down payment.”

Spain’s housing crisis has deepened over the years, consuming an increasing share of incomes and fueling public anger. While the problem exists in many countries, Spain’s youth and low-income workers have been particularly hard hit with rents and house prices far outpacing wages. More than two-thirds of adults under 34 live with their parents.

“I arrived in Madrid as a student and am now here as a worker; I’ve gone from having my parents pay my entire rent to still needing their help, even with a full-time job,” said Alejandro Garcia, 27. The one-bedroom flat he shares with his boyfriend costs €990 ($1,114) a month, representing a large chunk of their wages.

In the second quarter of 2026, Spanish house prices increased 12% from a year earlier, more than twice the European Union average. Spain has also built far fewer houses than other high-income countries over the last decade, and faces a shortage of about 750,000 homes according to the Bank of Spain.

Eldiario.es, a news website, reported that Sánchez will decide over the weekend whether to call an election, with Nov. 29 as a tentative date — legally, he has until July 2027 to call the election. Housing is a particularly sensitive issue for the left and could help mobilize its voters.

Belén Barrera, a university researcher, said she has little hope that the government passes effective measures.

“We cannot trust public institutions right now,” she said. “It’s a situation where the last straw has been reached.”

https://nationalpost.com/news/world/madrid-housing-protests-fuel-speculation-over-spanish-election

Retinal Neurodegeneration May Begin Before Prediabetes A1c Threshold

Retinal neurodegeneration may begin at A1c levels below the threshold currently used to define prediabetes, according to an analysis of more than 32,000 participants from the UK Biobank.

Investigators identified a turning point at approximately an A1c of 5.4 in the relationship between A1c and ganglion cell-inner plexiform layer (GCL-IPL) thickness, below both the 5.7 threshold used to define prediabetes and the 6.5 diagnostic threshold for diabetes. For total macular thickness, the estimated turning point was even lower, at approximately 5.3.

"This means that neuronal loss — and this is important — is taking place before current diagnostic criteria of diabetes," study lead Rafael Simó, MD, PhD, of the Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute, Barcelona, Spain, said in presenting the findings at the European Association for the Study of Diabetes (EASD) 2026 Annual Meeting.

To put the magnitude of the study findings into context, participants with diabetes had an approximately 1-µm reduction in GCL-IPL thickness compared with those with normal glucose levels, equivalent to about 6.5 years of physiological age-related retinal thinning. Among participants with prediabetes, total macular thickness was reduced by approximately 1.5 µm, comparable to at least 4 years of age-related retinal thinning.

Searching for an A1c Retinal Turning Point

The diagnosis of prediabetes and diabetes is based on glycemic thresholds associated with the development of microvascular disease. However, diabetic retinopathy is increasingly understood as a complex neurovascular disease, with neurodegeneration occurring early in its development, explained Simó.

There is "robust evidence," he said, that "the thinning of specific neuronal retinal layers can occur before overt microvascular abnormalities are detectable by ophthalmoscopic examination." If this is the case, "why do we have to wait until microvascular damage exists?" he asked.

Simó and colleagues therefore investigated whether retinal neurodegeneration might begin at A1c levels below current diagnostic cut offs, and if so, if they could identify an A1c threshold associated with the thinning of neuroretinal layers.

The analysis included 32,581 UK Biobank participants without a previous diagnosis of diabetes. Individuals with ocular diseases that could affect retinal thickness and neurodegenerative diseases were excluded. Retinal thickness was assessed using spectral-domain optical coherence tomography (OCT).

The researchers used restricted cubic spline analysis to examine nonlinear relationships between A1c and retinal thickness, with changes in slope evaluated using the Davies test. Analyses were adjusted for age, sex, mean arterial blood pressure, waist circumference, ethnicity, smoking status, and alcohol consumption. A sensitivity analysis was conducted in 20,380 participants with retinal data segmented according to the Early Treatment Diabetic Retinopathy Study system.

Retinal Thinning Before Prediabetes

The relationship between A1c and retinal thickness was nonlinear. In the GCL-IPL, retinal thickness initially increased slightly before reaching a turning point at an A1c of approximately 5.4, after which progressive thinning was observed as A1c increased. A similar pattern was observed across the neuronal retinal layers, whereas the retinal pigment epithelium behaved differently.

When total macular thickness was used as an integrated measure of all neuronal retinal layers, significant differences were seen not only between people with prediabetes and diabetes, but also between those with prediabetes and normal glucose levels. The estimated turning point for total macular thickness was at an A1c of approximately 5.3.

The findings support the concept that neural retinal changes can precede the vascular abnormalities traditionally associated with diabetic retinopathy.

"Our data extend and reinforce the concept that neurodegeneration is an early event in diabetic retinopathy," said Simó, adding that, overall, these findings "suggest that current diagnosis of diabetes based on A1c levels might need to be revisited."

What Might Drive the Changes?

The observational analysis could not establish that A1c levels around the identified turning points caused retinal neurodegeneration, nor do the turning points represent clinical thresholds at which an individual patient develops retinopathy, the researchers pointed out.

Further longitudinal research will be needed to determine whether retinal thinning at these lower A1c levels predicts subsequent diabetic retinopathy or diabetes and whether OCT-derived retinal measures could ultimately have a role in identifying individuals at increased metabolic or ocular risk.

Simó also emphasized that the study was not designed to establish the mechanism underlying the association. However, he highlighted insulin resistance as one potential contributor.

Previous experimental evidence suggests that intraocular insulin resistance could contribute to retinal neurodegeneration, he explained. Retinal neurons express insulin receptors, and impaired insulin signaling could affect neuronal survival. Simó also mentioned evidence linking systemic insulin resistance with thinning of neuronal retinal layers.

All this points "to insulin resistance as the most important element accounting for these findings," he said.

Could Earlier Intervention Help?

Commenting on the findings, session moderator Lena Thorn, MD, PhD, noted that the early appearance of neuroretinal thinning raised the question of whether earlier intervention could alter its course.

"You show that neuroretinal thinning occurs quite early in the disease process but is there any evidence that interventions at an earlier phase can slow down the thinning of the retina?" she asked.

Simó said there was evidence from experimental studies, but when Thorn asked specifically whether this had been demonstrated in humans, he replied with a no.

Simó disclosed relationships with Novo Nordisk, Abbott, Dexcom, Bayer, AstraZeneca, Menarini, and D-Sight. Thorn has declared no relevant disclosures.

https://www.medscape.com/viewarticle/retinal-neurodegeneration-may-begin-before-prediabetes-a1c-2026a10010xe

Autoimmune Researchers Seek Answers After Deaths in CAR T-Cell Trials

After three patient deaths and the indefinite pause of several clinical trials, questions are swirling over the future of chimeric antigen receptor (CAR) T-cell research for autoimmune diseases.

“I think this is an important moment in time for us,” Sayeef Mirza, MD, MPH, a hematologist/oncologist and cellular immunotherapy investigator at H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, told Medscape Medical News. “I think we are very excited with the advent and the discoveries of how beneficial CAR T is for lupus and scleroderma and multiple sclerosis, which are kind of the first poster children of autoimmune disease, being successfully treated with CAR T-cell therapy. But with these types of toxic and fatal events, it's a moment for pause to figure out what we can do as cellular therapists and hematologists and disease specialists. How can we work together to prevent this from happening?”

On August 24, Novartis announced it had suspended eight phase 2 and phase 1/2 trials of an autologous CD19-targeting product called rap-cel, developed to address autoimmune and neurologic diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), lupus nephritis, systemic sclerosis (SSc), and Sjögren disease. The pause was triggered by three cases of immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), all of which were fatal.

In a statement to Medscape Medical News, Novartis said the trials were on hold for the foreseeable future as the Swiss drugmaker worked with stakeholders to find answers.

“Novartis has temporarily paused rap-cel trials in immunology and neuroscience, following notification of serious IEC-HS events — a well-known [adverse event] in patients receiving CAR T-cell therapy,” the statement read. “We are engaging with the respective independent data monitoring and steering committees and actively sharing information with global health authorities. The safety and well-being of patients is of paramount importance to Novartis, and we remain committed to addressing the needs of these patient populations.”

Bristol Myers Squibb (BMS) subsequently implemented its own voluntary pause on studies for a rival CAR T-cell product, zola-cel, “out of an abundance of caution,” according to a report from Reuters. BMS did not respond to messages seeking additional comment.

The pauses stunned the research community, as CAR T-cells were hailed earlier this year as a potential game-changing therapy for autoimmune conditions. For example, a study published in January in Nature Medicine enrolled 24 patients (10 with SLE, nine with SSc, and five with idiopathic inflammatory myopathies), all of whom received a single infusion of zorpo-cel, a CAR T-cell product similar to zola-cel and rap-cel but that was not a part of the paused trials, after they stopped immunosuppressive treatments.

Potentially serious adverse events — cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) — were moderate or did not occur at all, respectively. Regarding efficacy, 22 of the participants achieved predefined efficacy endpoints, with nine of 10 patients with SLE reaching remission, all nine patients with SSc showing no disease progression, and four of five patients with idiopathic inflammatory myopathies reaching major or moderate response.

“[The study] suggests the feasibility, safety, and efficacy of zorpo-cel in three different autoimmune diseases and paves the way for conducting a pivotal study,” the study authors concluded.

The Root of the Problem

While originally identified as an oncology complication, IEC-HS has now become a focal point in rheumatology research. IEC-HS is generally defined as a pathologic immune reaction with features of secondary hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome, occurring independently from or as a worsening continuation of CRS.

“IEC-HS is a state of usually sterile inflammation where you have to intervene with immunosuppressive treatment regimens,” Georg Schett, MD, vice president of research and head of the department of medicine 3 at Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany, told Medscape Medical News. “IEC-HS is rare in cancer patients treated with CAR T cells — less than 5% — and it’s also rare in autoimmunity. It does not seem that there is an intrinsically higher risk for IEC-HS in autoimmune diseases.”

A real-world study published in May in Cancers examined 301 adults with hematologic malignancies treated with commercial CAR T-cell products. IEC-HS was identified in 14 individuals, representing an overall incidence of 4.7%. The complication developed across multiple hematologic malignancies, with onset occurring at a median of 10 days following infusion, emerging either during ongoing CRS or shortly after its resolution.

Still, the two conditions are clinically distinct. CRS is a direct outcome of infused CAR T cells engaging their target antigen, leading to the large-scale activation of interleukin (IL)-6, IL-10, and TNF-alpha. IEC-HS involves a pathologic feedback loop between CAR T cells and host macrophages.

Further, CRS usually peaks in the first week post-infusion, while IEC-HS typically manifests after CRS has crested or resolved. According to guidelines from the American Society for Transplantation and Cellular Therapy, although CRS is a primary risk factor for IEC-HS, the latter condition operates as a distinct phenomenon rather than simply “severe CRS.”

According to Daniel Lee, MD, associate professor and director of pediatric hematopoietic stem cell transplantation and cellular therapy at the University of Virginia (UVA) School of Medicine and the UVA Comprehensive Cancer Center, Charlottesville, Virginia, “we simply do not know enough about T-cell biology and its interplay with the rest of the immune system, particularly when it has been previously exposed to other immuno- or chemotherapies, to be able to predict [CAR T-cell] expansion for a particular patient.”

“This is not to say that the approach should be abandoned, just that we need to dive deeper to understand more,” Lee told Medscape Medical News. “What we do know when it comes to CAR T-cell toxicities, including IEC-HS, is that they result from an uncontrolled, supraphysiologic activation of multiple components of the immune system. Macrophages and other myeloid-derived cells are implicated in particular. The more [CAR T-cell] activation and expansion that occurs, the more the bystander immune system is activated, which can then perpetuate the process by further activating CAR T cells. The lack of our ability to control CAR T cells once infused is at the root of the problem.”

Seeking Answers

That uncertainty is leading to questions over what, if anything, can or should change in autoimmune CAR T-cell trials moving forward. Both Novartis and BMS used rapid manufacturing platforms to generate more CAR T cells more quickly. This approach has emerged as an early potential explanation for the adverse events.

“Faster production methods shift the proliferation of therapeutic cells from ex vivo to in vivo, which may precipitate a hyperinflammatory state,” Schett said. “Hence, modifying the production process or administering lower cell numbers may be critical.”

This is easier said than done, Schett added, particularly in light of the serious and highly time-sensitive oncologic indications the cell products are in part designed to combat.

“Fast CAR T-cell production is important in acute lymphoblastic leukemia because this disease is rapidly progressing and kills the patient,” Schett explained. “In autoimmunity, you don't have such hurry. It’s usually not a matter of a few weeks. And so, I think it is obviously better to have a rather safe product with low risk of inflammatory toxicities.”

Experts cautioned, however, that it was too early to speculate on a reason behind the toxicities and that the causes are likely multifactorial.

“Rapid manufacturing has been shown to increase the proliferative capacity and cytokine production of CAR T cells, which may lead to higher efficacy but also incidence of side effects,” Aimee Payne, MD, PhD, Herbert and Florence Irving Professor and Chair of Dermatology at Columbia University Vagelos College of Physicians and Surgeons, New York, told Medscape Medical News.

“But we need more details to know all the contributing factors,” she said. “For example, what disease indication did the IEC-HS cases occur in, was diagnosis delayed, were there any other contributing factors such as fever, occult infection or viral reactivation, or possibly rare genetic mutations that may have increased the risk of IEC-HS occurring? These are the data we hope to learn as soon as possible so that the field can advance safely.”

Patient selection as well as issues like dosage considerations could also be pieces of the puzzle, experts noted.

“With three deaths due to IEC-HS, one must re-examine the eligibility criteria, among many other factors, for these autoimmune trials,” Lee said. “No doubt the companies are doing that. Equally as important is to reassess the product being given, starting with dose. Analyzing expansion kinetics in patients … and partnering this with CAR T phenotype (before and after infusion), [and analyzing] cytokine/chemokine and toxicity data may reveal some important correlates for enhanced toxicity risk. The protocol and/or product can then be modified accordingly.”

Researchers pointed to the complex relationship between the disease and the treatment.

The state of hyper-inflammation present in patients with rheumatologic or other autoimmune diseases has the potential to convey a “higher risk of HLH, but the CAR T cells that we give them are also requiring expansion, and there might be some interplay between the host immune system and the new CAR T cells that are being put in, whether they’re allogeneic or autologous,” Mirza said. “And if they're rapidly manufactured and they’re super-robust and super-potent type of immune cells going into a hyper-inflamed environment, you have all the stars aligned for a very toxic outcome. And so, the treatment for that is more immune suppression to calm the immune system down.”

Schett emphasized that cross-functional teamwork was essential in identifying and responding to any problems that emerge in patients undergoing CAR T-cell therapy.

“I think is very important to have good monitoring and a skilled team,” Schett said. “I think at the end, such complications may be avoided when there is a rigid patient selection. So, if one is not sure if there is concomitant infection or the inflammation level due to autoimmune disease is high or the patient has fever, just take your time, evaluate the patient carefully before you start. I think these considerations are important to avoid such reactions. CAR T-cell treatment can be life-changing — a single infusion can stop the disease. But of course, this treatment is not like an aspirin. It’s actually something you have to give into the hands of a skilled team, and I think that’s very important for consideration in the future.”

Mirza reported consultancy/advisory/honoraria support from BMS, Gilead Sciences, Guidepoint, Prime Education, Curio Science, and OncLive, and he is part of the BMS speaker’s bureau. Schett disclosed financial relationships with BMS, Cabaletta Bio, Janssen Biotech, Kyverna, and Novartis. Lee holds a patent related to mitigating CAR T-cell toxicities. Payne is co-founder of Cabaletta Bio.

https://www.medscape.com/viewarticle/autoimmune-researchers-seek-answers-after-deaths-car-t-cell-2026a10010xi

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