The biological connection between a pregnant woman and her developing baby—the human maternal–fetal interface—is a specialized, transient organ composed of uterine cells from the mother and fetal cells that acts as a barrier, supports fetal growth, and maintains the mother’s health. The cellular complexity of the maternal-fetal interface has limited scientists’ ability to study how healthy pregnancies develop and why complications arise. The underlying cellular, molecular, and spatial programs of the interface—which forms about a week after fertilization and lasts until birth—has remain incompletely defined.
Now, the human maternal–fetal interface has been mapped in unprecedented detail by scientists at the University of California, San Francisco (UCSF), revealing new cell types and providing insights into conditions such as preeclampsia, preterm birth, and miscarriage.
“By examining this tissue cell by cell across pregnancy, we can begin to understand both normal development and what may go wrong,” said Susan J. Fisher, PhD, professor of obstetrics, gynecology, and reproductive sciences at UCSF.
The team generated a comprehensive atlas of the human maternal–fetal interface across normal pregnancies, from early gestation to term. The researchers did this by “integrating large-scale paired single-nucleus transcriptomic and chromatin accessibility profiling with submicrometer-resolution spatial transcriptomics and CODEX multiplex protein imaging.”
Using these tools, the researchers analyzed about 200,000 individual cells and compared them with nearly one million cells in their original positions within the uterine and placental tissue. This enabled them to identify different cell types, track how they develop, and see how they are linked to pregnancy complications.
“This work gives us a much clearer picture of this critical region than ever before,” said Jingjing Li, PhD, associate professor in UCSF’s Department of Neurology and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research.
The atlas revealed a previously unknown maternal cell type located where fetal placental cells first enter the uterus. These cells appear to regulate how deeply placental cells invade uterine tissue, a process that is essential for establishing blood flow to the fetus. The researchers found that these cells carry a cannabinoid receptor, and exposure to cannabinoid molecules caused them to further restrict placental cell invasion.
“Population studies have linked cannabis use during pregnancy to poorer outcomes,” said Cheng Wang, PhD, a postdoctoral fellow at UCSF. “This cell type may help explain the biological basis of that association.”
To understand how complications arise, the team integrated genetic data from more than 10,000 patients. They mapped genetic risk signals for conditions including preterm birth, preeclampsia, and miscarriage onto regulatory regions of DNA that control gene activity. This approach allowed the researchers to identify the specific cell types and states most strongly associated with each condition.
The team then focused on preeclampsia, a potentially life-threatening disorder marked by sudden high blood pressure. They found that the most affected cell types are involved in remodeling the mother’s uterine blood vessels, a process required to supply adequate blood to the placenta. The findings suggest that preeclampsia may result from disrupted communication between maternal and fetal cells that normally coordinate this process.
Having established a detailed map of healthy pregnancies, the researchers plan to study complicated pregnancies to identify potential targets for treatment.
This is today’s edition of The Download, our weekday newsletter that provides a daily dose of what’s going on in the world of technology.
Desalination plants in the Middle East are increasingly vulnerable
As the conflict in Iran has escalated, a crucial resource is under fire: the desalinization technology that supplies water in the region.
President Donald Trump has threatened to destroy “possibly all desalinization plants” in Iran if the Strait of Hormuz is not reopened. The impact on farming, industry, and—crucially—drinking in the Middle East could be severe. Find out why.
—Casey Crownhart
This story is part of MIT Technology Review Explains, our series untangling the complex, messy world of technology to help you understand what’s coming next. You can read more from the series here.
AI is changing how small online sellers decide what to make
For small entrepreneurs, deciding what to sell and where to make it has traditionally been a slow, labor-intensive process. Now that work is increasingly being done by AI.
Tools like Alibaba’s Accio compress weeks of product research and supplier hunting into a single chat. Business owners and e-commerce experts say they’re making sourcing more accessible—and slashing the time from product idea to launch.
The gig workers who are training humanoid robots at home
When Zeus, a medical student in Nigeria, returns to his apartment from a long day at the hospital, he straps his iPhone to his forehead and records himself doing chores.
Zeus is a data recorder for Micro1, which sells the data he collects to robotics firms. As these companies race to build humanoids, videos from workers like Zeus have become the hottest new way to train them.
Micro1 has hired thousands of them in more than 50 countries, including India, Nigeria, and Argentina. The jobs pay well locally, but raise thorny questions around privacy and informed consent. The work can be challenging—and weird. Read the full story.
—Michelle Kim
This is our latest story to be turned into an MIT Technology Review Narrated podcast, which we’re publishing each week on Spotify and Apple Podcasts. Just navigate to MIT Technology Review Narrated on either platform, and follow us to get all our new content as it’s released.
The must-reads
I’ve combed the internet to find you today’s most fun/important/scary/fascinating stories about technology.
1 Anthropic’s new model found security problems in every OS and browser Claude Mythos has been heralded as a cybersecurity “reckoning.” (The Verge) + Anthrophic is limiting the rollout over hacking fears. (CNBC) + It’s also launching a project that lets Mythos flag vulnerabilities. (Gizmodo) + Apple, Google, and Microsoft have joined the initiative. (ZDNET)
2 Iranian hackers are targeting American critical infrastructure Their focus is on energy and water infrastructure.(Wired) + They’re targeting industrial control devices. (TechCrunch)
3 Google’s AI Overviews deliver millions of incorrect answers per hour Despite a 90% accuracy rate. (NYT $) + AI means the end of internet search as we’ve known it. (MIT Technology Review)
4 Elon Musk is trying to oust OpenAI CEO Sam Altman in a lawsuit As remedies for Altman allegedly defrauding him. (CNBC) + Musk wants any damages given to OpenAI’s nonprofit arm. (WSJ $)
5 ICE has admitted it’s using powerful spyware The tools that can intercept encrypted messages. (NPR) + Immigration agencies are also weaponizing AI videos. (MIT Technology Review)
6 Greece has joined the countries banning kids from social media Under-15s will be blocked from 2027. (Reuters) + Australia introduced the world’s first social media ban for children. (Guardian) + Indonesia recently rolled out the first one in Southeast Asia. (DW) + Experts say they’re a lazy fix. (CNBC)
7 Intel will help Elon Musk build his Terafab in Texas They aim to manufacture chips for AI projects. (Engadget) + Musk says it will be the largest-ever semiconductor factory. (Engadget) + Future AI chips could be built on glass. (MIT Technology Review)
8 TikTok is building a second billion-euro data center in Finland It’s moving data storage for European users. (Reuters) + Finland has become a magnet for data centers. (Bloomberg $) + But nobody wants one in their backyard. (MIT Technology Review)
9 Plans for Canada’s first “virtual gated community” have sparked a row The AI-powered surveillance system has divided neighbors. (Guardian) + Is the Pentagon allowed to surveil Americans with AI? (MIT Technology Review)
10 The high-tech engineering of the “space toilet” has been revealed Artemis II is the first mission to carry one around the world. (Vox)
Quote of the day
“This case has always been about Elon generating more power and more money for what he wants. His lawsuit remains nothing more than a harassment campaign that’s driven by ego, jealousy and a desire to slow down a competitor.”
—OpenAI criticizes Musk’s legal action in an X post.
One More Thing
USWDS
Inside the US government’s brilliantly boring websites
You may not notice it, but your experience on every US government website is carefully crafted.
Each site aligns an official web design and a custom typeface. They aim to make government websites not only good-looking but accessible and functional for all.
A place for comfort, fun and distraction to brighten up your day. (Got any ideas? Drop me a line.)
+ Rejoice in the splendor of the “Earthset” image captured by Artemis II. + Meet the fearless cat chasing off bears. + This document vividly explains what makes the octopus so unique. + Revealed: the rhythmic secret that makes emo music so angsty.
Dynamic42 and EPO (Experimental Pharmacology and Oncology), both based in Germany, report that they are addressing the limited availability of preclinical models in brain cancer research by forming a strategic collaboration that focuses on bringing organ-on-chip technologies “closer to the core of preclinical drug development.”
The partnership combines Dynamic42’s organ-on-chip platforms with EPO’s expertise in translational oncology and access to well-characterized tumor models and patient-derived material. Together, the teams are developing experimental setups designed to reflect human tumor biology more closely and generate data that translates more reliably into clinical outcomes.
The first joint projects target glioblastoma and the blood–brain barrier (BBB). Using Dynamic42’s human-based BBB-on-chip model, the partners will explore how differences between human and non-human BBB-biology can influence therapeutic responses, which is a major factor for the limited activity of brain cancer drugs.
“Too often, critical decisions in drug development rely on data that do not fully reflect human biology,” said Thomas Sommermann, PhD, head of cancer research at Dynamic42. “We want to change that. By bringing human-based models earlier into the process, we can sharpen decision-making and reduce late-stage failure risks.”
“For us, this collaboration is about strengthening the translational link,” added Jens Hoffmann, CEO at EPO. “Integrating advanced in vitro systems allows us to look at tumor biology from a different angle and to build robust experimental in vivo strategies.”
The collaboration is designed as a complementary approach that connects established preclinical in vivo expertise with emerging human-based in vitro technologies. It supports more targeted, biology-driven research strategies and the principles of the 3Rs (Replace, Reduce, Refine), contributing to the ongoing shift toward more human-relevant experimental systems.
Beyond joint research, the partnership includes model development activities, elaboration of commercialization strategies, and close scientific exchange, including collaboration between early-career researchers from both organizations.
Dynamic42 and EPO will jointly present the first results of their collaboration at the American Association for Cancer Research® Annual Meeting 2026. Both companies plan to expand the collaboration further, exploring additional indications and extending the use of organ-on-chip technologies across different areas of drug development.
It’s the leading risk factor for the leading cause of death in the United States and around the world: high blood pressure, the prime mover in heart attacks and strokes.
High blood pressure is treatable, but despite having access to effective and affordable medications, more than half of Americans still have uncontrolled hypertension, with rates going up in sync with adverse social determinants of health.
There is no doubt that autologous chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of serious blood cancers. A significant proportion of advanced-stage blood cancer patients who failed to respond to previous therapies now go into remission with this treatment, with some remaining cancer-free in the long term.
However, despite their success, these immunotherapies have significant disadvantages. Although CAR T-cell therapies have essentially rescued advanced-stage patients who previously would only have been offered palliative care, serious side effects such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS) are associated with the treatment.
All seven CAR T-cell therapies approved by the U.S. Food and Drug Administration (FDA) since August 2017 are autologous cell therapies, wherein the patient’s own T cells must be extracted and genetically engineered in the lab to produce cancer-targeting CAR T cells that are reinfused into the patient to fight the cancer.
Unless they live near a major cancer center or company with the relevant expertise and lab capacity in-house, many eligible patients miss out on the therapy because the wait time is too long or the whole process is too expensive. Patients must also be admitted to the hospital to undergo lymphodepletion chemotherapy before receiving the final infusion to allow the infused cells to expand, persist, and work better.
“It’s just simply too expensive, too complex to manufacture, and has all kinds of logistical issues that translate to limited patient access,” explained Maurits Geerlings, MD, co-founder, CEO, and president of in vivo CAR T-cell therapy biotech NanoCell Therapeutics, which has offices in Pennsylvania and Utrecht.
“Also, importantly, the batch capacity in highly specialized hospitals is so limited that altogether maybe 10% of patients that are eligible effectively get access to CAR T-cell therapy in the Western world.”
Maurits Geerlings, MD Co-founder, CEO NanoCell Therapeutics
Initially, after the first ex vivo, autologous CAR T-cell therapies like Novartis’s Kymriah and Kite’s Yescarta were approved in 2017, the field looked to develop “off-the-shelf” allogeneic therapies made from donor cells that would overcome some of the issues with autologous CAR T-cell therapies.
Despite the best efforts of a number of companies and researchers, no allogeneic CAR T-cell therapies have yet reached the market, although some companies like Allogene have reached Phase II trials. This is likely due to a few factors, such as adverse events linked to the rejection of donor cells, complex engineering problems, and the small margin of benefits of allogeneic over autologous CAR T-cell therapies.
Instead, over the last couple of years, the focus of the field has moved towards developing next-generation in vivo CAR T-cell therapies. Until recently, vectors or nanoparticles that could hit T cells precisely, safely, and predictably enough in humans to justify skipping ex vivo engineering were simply not available, but this is now changing.
In vivo CAR T-cell therapy uses the patient as a bioreactor. Upon injecting an engineered treatment carried by a vector such as a lentivirus or a lipid nanoparticle (LNP), it programs the patient’s T cells to attack either the cancer or autoreactive B cells in the case of autoimmune disease.
The field is still young, but initial clinical results reported last year in multiple myeloma blood cancer by Kelonia Therapeutics and in the B cell-driven autoimmune disease systemic lupus erythematosus by MagicRNA, as well as from EsoBiotec and academic labs, are promising.
Kevin Friedman, PhD Co-founder, CEO Kelonia Therapeutics
“It’s early days, so I don’t want to overinterpret the data. It’s also only in four patients, but what we are seeing is substantially better than what ex vivo CAR T cells have shown from an efficacy perspective,” emphasized Kelonia CEO and co-founder Kevin Friedman, PhD.
Indeed, this early success seems to have prompted intense investor and big pharma interest in the field. Since March 2025, when EsoBiotec was acquired by AstraZeneca, at least four other in vivo CAR T cell biotechs have been acquired, including Capstan Therapeutics by AbbVie and Interius BioTherapeutics by Kite/Gilead.
Whether in vivo CAR T-cell therapy will truly be the future of the field remains to be seen, but its convenience, economic viability, and the fact that it is effectively an “off-the-shelf” therapy that does not require lymphodepletion make it an attractive prospect for many.
Credit: Kelonia
Lentiviral vectors: Sticking with a known quantity
Five of the seven FDA-approved autologous CAR T-cell therapies, including Kymriah, use lentiviral vectors in the lab to engineer a patient’s T cells and transform them into CAR T cells.
Many of the most advanced companies in the in vivo CAR T- cell therapy space are applying similar technologies and using lentiviral vectors to target and transform T cells, but inside the body rather than in the lab.
Kelonia, which is based in Boston, is a leader in the in vivo CAR T-cell space and has already started clinical trials with its lead candidate KLN-1010 for the treatment of patients with relapsed and refractory multiple myeloma.
“It’s essentially delivering a fully human anti-BCMA (B cell maturation antigen) CAR to T cells, to reeducate them by expressing this anti-BCMA CAR inside the body to fight their tumor cells. Just like Abecma, or Carvykti, but it’s all done inside the body,” explained Friedman.
At the American Society of Hematology Annual Meeting in December last year, the company presented early Phase I results from four patients with relapsed and treatment-resistant myeloma who were treated with KLN-1010.
Although the study was small, the results were promising, with all four patients showing 100% minimal residual disease-negative response rate at follow-up and a lower rate of side effects than approved autologous CAR T-cell therapies.
“With our data and the efficacy and the safety profile that we’re seeing, this has a real shot at getting out of the major medical centers and into the community hospitals where the patients live, so they don’t have to travel to major medical centers,” said Friedman.
“Doctors can potentially treat patients in their own community and get access to the 90% of myeloma patients who, right now, despite the profound clinical benefit that CAR T cells provide, cannot be treated.”
Ryan Larson, PhD Senior Vice President Umoja Biopharma
Umoja Biopharma is another biotech using lentiviral vectors to develop in vivo CAR T-cell therapies. “We have three different products in the clinic currently. Two of those products are in B-cell malignancies, and one of the products is in autoimmune disease. And we’re making really great progress in enrolling patients across those studies,” said Ryan Larson, PhD, senior vice president and head of research at Umoja, although the Seattle-based company has not yet released any results from its Phase I studies.
Although Umoja is using lentiviral vectors, it has built in a rapamycin-activated cytokine receptor, which essentially acts as a booster switch for the engineered T cells in cancer patients while slightly dampening the rest of the immune system.
“It allows us to deliver a controlled pro-survival signal selectively to our CAR T cells in vivo,” explained Larson. “We’re able to potentiate persistence in a controlled manner in our in vivo generated CAR T cells with this rapamycin-activated cytokine receptor to drive persistence and ongoing immune surveillance, thus driving the key durable outcomes in oncology specifically.”
The requirements for autoimmune disease patients are different from those of advanced cancer patients, with a greater focus on safety. Long-term depletion of B cells is also not ideal, with the aim being to reset the immune system by getting rid of autoreactive B cells and replacing them with healthy ones.
“You’re eliminating all of the autoreactive repertoire and replacing it with a normal B cell repertoire, thus driving, ideally, a durable response wherein those autoimmune disease patients are no longer reliant on all the various immunosuppressants that are typically used to treat autoimmune disease,” said Larson.
Kite Pharma, now owned by Gilead and headquartered in California, was a pioneer in the autologous CAR T-cell therapy space. It developed Yescarta, one of the first two autologous CAR T-cell therapies approved by the FDA to treat blood cancers in 2017. Kite recently acquired Interius BioTherapeutics, a biotech in the lentiviral in vivo CAR T-cell space, for $350 million.
Priti Hegde, PhD Senior Vice President Kite Pharma, a Gilead Company
“The reason why we moved forward with Interius was that the clinical proof of concept for lentiviral-based delivery systems is far more advanced than for LNP-based systems,” said Priti Hegde, PhD, senior vice president and global head of research at Kite. “We were really excited to see that translation of the pharmacokinetics from an ex vivo platform to an in vivo platform.”
While lentiviral vectors are arguably “tried and tested” in the CAR T-cell space, there are some disadvantages associated with using them. For example, they can be hard to produce, implying that it is expensive and challenging to scale up manufacturing.
This is something both Umoja and Kelonia seem to have addressed, however. “We actually are quite unique from a biotech perspective in that we have our own, wholly owned manufacturing facility … It’s really allowed us to have a true pipeline from an in vivo cell therapy development perspective,” said Larson. “We’re actively working in our early phase clinical trials in a manufacturing setting that we know is scalable to commercial readiness.”
Kelonia does not do all its manufacturing in-house, but Friedman said that they have worked hard to develop a system that can be scaled. “Manufacturing is complicated. We like to think that we were thoughtful about our manufacturing approach, but it’s challenging generating these particles, these complicated medicines for Phase I use. We did it, though, and we now have a very reliable and scalable manufacturing process.”
Another potential risk linked to lentiviral and other viral vectors is that there is a small but significant risk of the vector inducing unwanted mutations in the DNA of target cells.
“Viral vectors have a propensity to integrate in transcriptionally active gene regions where you don’t want to go, because that enhances the mutagenesis risk,” noted NanoCell’s Geerlings.
Taking the non-viral route
Not everyone working to develop in vivo CAR T-cell therapies is using viral vectors. The second main route that companies and researchers are following to develop these cell and gene therapies is to use mRNA encapsulated in an LNP.
Last September, Shenzhen-based Chinese biotech MagicRNA published data from a Phase I trial of its in vivo mRNA and LNP-based CAR T-cell therapy in five patients with systemic lupus erythematosus. Similar to in Kelonia’s cancer trial, the results were promising. However, larger studies are needed for more conclusive results, as the sample size was small. But rapid, near-complete B cell depletion was seen for up to 10 days with no significant side effects like serious cytokine release syndrome or ICANS.
Since the pandemic, the use of mRNA therapeutics has become much more mainstream. For example, both of the prevalent vaccines against COVID-19 use a combined mRNA–LNP approach. In in vivo CAR T-cell therapy, the LNPs are used to take CAR-encoding mRNA to the right target cells in the body. Once inside a T cell, the LNP breaks apart and releases the mRNA into the cytoplasm. The cell’s protein synthesis machinery reads the mRNA and makes the correct CAR protein, which is then added to the surface of that T cell.
Aera Therapeutics, founded by CRISPR pioneer Feng Zhang, PhD, and based in Cambridge, Massachusetts, takes a combined mRNA–LNP approach to in vivo CAR T-cell therapy development, with a focus on treating B cell-mediated autoimmune disease.
Akin Akinc, PhD CEO, Aera Therapeutics
“We were really focused on autoimmune indications, so we said, ‘Let’s try to build a product profile that’s a great fit for that,’” explained Akin Akinc, PhD, who is CEO at Aera.
“You have the risk of insertional mutagenesis with lentiviral vectors. Even if those rates are small, they’re not zero … So that’s why we thought an mRNA–LNP approach, where there’s no chance of insertion, is theoretically a more attractive approach.”
Aera has not yet moved into clinical studies but reported preclinical data for its therapy candidate AERA-109 in non-human primates at the American Society of Hematology Annual Meeting at the end of last year. They showed potent and durable B cell depletion across different tissues in the body.
One potential disadvantage of using a combined mRNA–LNP approach, particularly for treating cancer, is that it is unlikely to last as long as a lentiviral approach. As this could be potentially advantageous in people with autoimmune disease, where B cell depletion does not need to occur over such a long period of time, it seems to be the most common method followed by companies designing in vivo CAR T-cell therapies for autoimmune conditions.
“Our therapeutic goal is to go in and clear out the B cells that exist in the body, both in the periphery and the tissues, and then allow them to repopulate. If we achieve that immune reset, then that’s all that we can do,” said Akinc.
Scott Barros, Head of Early Development, Akin Akinc, Chief Executive Officer, Bill Querbes, Chief Scientific Officer.
“Then the question is, is there going to be a relapse 12–18 months later? But so long as we clear out all the B cells, which happens pretty quickly, I think there’s no benefit to having the CAR T cells hanging around for longer, because at that point you’ve done the job. Then it’s about whether or not that remission is going to persist.”
NanoCell Therapeutics is also taking a non-viral approach to developing in vivo CAR T-cell therapy for treating B-cell malignancies, but is using DNA instead of RNA. The candidate has not yet reached the clinic, but it has achieved good preclinical results and will soon be tested in non-human primates.
Similar to Aera, NanoCell packages its therapy in targeted LNPs. However, these carry a minicircle DNA that encodes the CAR information and an mRNA transposase that allows the DNA to integrate into the target cell genome.
“We still remain, I think, pretty much in the lead as a company delivering non-viral DNA, because it is very difficult … We see an opportunity for us to actually make a breakthrough there,” said Geerlings.
“The nuclear membrane of the cell is such a barrier. You need to find an opportunity to open it up and to be just in time with your DNA in a way that is not triggering an innate immune response. You also need to have a mechanism by which that DNA can integrate, because otherwise, you will end up having an episomal expression of your DNA.”
The approach taken by NanoCell is definitely at an earlier stage than the lentiviral and mRNA–LNP approaches that are already generating clinical data, but there are a couple of other companies working on similar products, like Stylus Medicine and CPTx. If it works, then this approach has the promise of ruling out problems with viral vectors, such as manufacturing difficulties. It would also theoretically generate longer-lasting and more durable treatment effects than could be achieved with mRNA.
What’s next for CAR T-cell therapy?
It seems that we are on the cusp of next-generation in vivo CAR T-cell therapies, although the studies published so far have all been small and it remains to be seen if the current buzz in the space is based on hype or reality.
“I do think that in vivo will go from a platform with initial proof-of-concept to broad applicability faster than perhaps ex vivo platforms did,” said Hegde. “But we have a lot of scientific questions. For example, in the absence of lymphodepletion, can an in vivo platform give you the depth and durability of response that an ex vivo platform does?”
There is a lot of interest in whether safer and more accessible in vivo CAR T-cell therapy can make this treatment approach more appealing to people with B-cell-mediated autoimmune conditions than autologous CAR T-cell approaches. The initial clinical results are good, but questions remain about how long the results will last.
“I think these are going to work, but we’re going to learn things that allow us to make second-generation products that are even better and even more potent,” said Akinc.
On the cancer side of things, most companies developing in vivo CAR T-cell therapies for oncology indications are sticking with blood cancers against which autologous CAR T-cell therapies have already been shown to be efficacious.
“I think we’ll continue to see strong proof of concept in de-risked indications like the hematologic malignancies over the next year,” said Larson. “Over the next two years, I think we’re going to be closely watching the field for durable outcomes in oncology and the ability to drive immune reset in autoimmune disease that then translates to durable remissions in autoimmune disease patients.”
A big question on everyone’s mind is whether this new technology could help overcome some of the hurdles that prevent CAR T-cell therapy from being successful at treating “solid” tumors, such as working out how to overcome diverse tumor microenvironments.
“I think there’s great potential in solid tumors. One reason why we went with Interius was [that] we think that the application of the in vivo platforms could really break open the problems that we perhaps had in solid tumors with ex vivo CAR T cells,” said Hegde.
“The nice thing about the in vivo space is you can put whatever targeting antigen you want on the virus to go to a specific cell type. So it’s really up to your imagination, how you want to design an in vivo CAR T cell.”
Dispatch Bio is also in the CAR T-cell therapy space, but is targeting solid tumors rather than developing in vivo CAR T cells. The company is based in Philadelphia and was co-founded by Carl June, MD, one of the pioneers of CAR T-cell therapy.
The technology they are developing is a two-component system, in which a human-specific adenovirus designed to infect cancer cells, but not healthy tissue, is used to “paint” the tumor cells so that a CAR T cell can more easily home in on the cancer and destroy it.
Barbra Sasu, PhD Chief Scientific Officer Dispatch Bio
“The virus gets into the tumor microenvironment and then, because it’s a virus, creates an inflammatory condition. When it does that, it’s immediately more supportive for T cells,” explained Dispatch chief scientific officer Barbra Sasu, PhD.
“We’re doing what T cells can’t do for themselves. We’re expressing a target and directing them to kill what we want them to kill. We’re also adding a cytokine to support them and, actually, the endogenous immune system too.”
The two-part approach is very new, so Sasu and colleagues are testing the system using a known autologous CAR T-cell therapy approach. But she says that the system is potentially very flexible and could allow a wide range of therapies, including in vivo CAR T-cell therapies, to be combined with the viral targeting approach if they prove effective.
“What we wanted to do was to start with something that we felt we understood very well. We also had the benefit in our first program of being able to work with people who’ve already developed CAR T-cell therapies,” said Sasu. “That’s a big advantage because [when] coming in with a two-component system, it’s good if you don’t have to refine both parts at once.”
Another CAR T-based approach being developed by Kite and others in this space is logic gating, which is the development of IF, AND, and NOT switches to allow much more refined control of CAR T-cell therapies by clinicians and potentially increase effectiveness in complex solid tumors.
“We’re really interested in exploring the logic gating space and what it can do to deliver CAR T cells more safely, especially in solid tumors, where the antigens aren’t as broadly homogeneously expressed,” said Hegde.
Helen Albert is senior editor at Inside Precision Medicine and a freelance science journalist. Prior to going freelance, she was editor-in-chief at Labiotech, an English-language, digital publication based in Berlin focusing on the European biotech industry. Before moving to Germany, she worked at a range of different science and health-focused publications in London. She was editor of The Biochemist magazine and blog, but also worked as a senior reporter at Springer Nature’s medwireNews for a number of years, as well as freelancing for various international publications. She has written for New Scientist, Chemistry World, Biodesigned, The BMJ, Forbes, Science Business, Cosmos magazine, and GEN. Helen has academic degrees in genetics and anthropology, and also spent some time early in her career working at the Sanger Institute in Cambridge before deciding to move into journalism.
