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We’re back with more data from the AACR meeting! Among the highlights today: a first look at a drug Merck acquired from China, a fascinating but potentially controversial use for CAR-T, and American oncology’s geography problem. Don’t forget: Tuesday night we will host a live event in San Diego, and we also have a virtual recap of the AACR conference on Thursday.
CAR-T shows deep response in smoldering myeloma
In an early phase trial, investigators at Dana-Farber Cancer Institute treated 20 high risk smoldering multiple myeloma patients with Carvykti, a BCMA directed CAR-T therapy. The idea was to use the immunotherapy on patients with the multiple myeloma precursor condition, hoping to prevent the active cancer in patients at high risk of progression.
Pfizer executive Andrew Baum, a former analyst at the investment bank Citi who joined the company in June 2024 to redirect its strategic approach, has left his role as an executive vice president and chief strategy and innovation officer, the company confirmed Monday. He will continue as an adviser to Pfizer CEO Albert Bourla until the end of the year.
Pfizer and sources familiar with the matter described the move as stemming from both a sense that Baum had accomplished what he set out to do and a streamlining of Pfizer’s operations.
“Pfizer regularly evaluates its operations to ensure it is best positioned to deliver on the company’s business in the near-term and beyond,” the company said in a statement. It said that organizational and leadership changes would “position Pfizer to move faster, make clearer decisions, and advance innovation across the enterprise.”
Damage to the liver in patients developing end-stage liver disease has become too severe for the organ’s normally extraordinary regenerative capacity to repair or compensate for that damage. Once this point of no return has been reached the only option is an organ transplant. However, donor livers are in high demand and very limited supply.
Ambitious efforts are on the way that eventually could enable the engineering of entire implantable liver organs. However, the maximum size of laboratory-engineered liver constructs remains limited and cannot yet provide therapeutic benefits for patients. A research team at the Wyss Institute at Harvard University, Boston University, and MIT has now approached this important problem from a different angle.
“We asked if it would be possible to first implant a small-scale liver construct and then drive it to expand in the body following its engraftment,” said Christopher Chen, MD, PhD, a Wyss Institute core faculty member and the William Fairfield Warren Distinguished professor of biomedical engineering and director of the Biological Design Center at Boston University. “A sufficiently grown, functional ‘satellite liver’ could immediately relieve the metabolic burden in a damaged liver and help bridge the time until a transplant becomes available.”
Chen co-led the research together with associate faculty member Sangeeta Bhatia, MD, PhD, who is the John J. and Dorothy Wilson Professor of Health Sciences and Technology and of Electrical Engineering and Computer Science at the Koch Institute for Integrative Cancer Research at MIT, and a Howard Hughes Medical Institute investigator. Chen is also a leader of the Wyss Institute’s 3D Organ Engineering Initiative, and team lead of the recently awarded ARPA-H PRINT-supported ImPLANT project, which focuses on whole organ liver engineering at the Wyss and collaborating institutions.
The project, spearheaded by Amy Stoddard, PhD, (MIT ’25), who developed the approach in her doctoral research and then as a postdoctoral fellow, integrates tissue engineering and synthetic biology tools in a genetic strategy the team has named “bioengineered on-demand outgrowth via synthetic biology triggering,” or BOOST. By specifically rewiring the gene expression of primary liver hepatocytes and supportive fibroblast cells, the scientists were able to effectively switch on a tissue growth program in small, engineered liver constructs after their implantation into mice.
“Using engineered liver tissue as a proof-of-concept application, we integrated synthetic biology and tissue engineering tools to build liver tissues that can be expanded on-demand after implantation in vivo,” the team reported in their published paper in Science Advances, which is titled “Synthetic control of implanted engineered liver tissue growth.” In the paper they concluded “In this study, we define the first steps toward an unconventional approach to cell therapy scale-up: engineering a small construct and then inducing it to grow in situ … “This strategy, which we have named BOOST, could provide several key advantages, including circumventing the need for large quantities of cellular raw materials and bypassing the formidable challenge of generating a rapidly perfusable construct that can survive the engraftment period.”
The authors wrote, “Organ transplant is currently the only curative treatment for patients with end-stage organ failure, yet this therapy is inaccessible to many due to the paucity of organs available for transplant.” And while significant progress has been made in the field of engineering tissue-based cell therapies that could represent alternatives, or bridges to transplant, they acknowledge, “… scaling of these constructs to sizes of therapeutic relevance remains a barrier to clinical translation.”
In order to address current challenges associated with fabrication, Chen and colleagues looked at the problem from different angle, asking whether it would be possible to first implant a small-scale construct and then trigger it to expand in situ, after its engraftment into the host.
To be able to induce growth of an implanted small liver constructs in situ within a recipient’s body the researchers first needed to identify the relevant cues that would allow them to do so. “A key first step toward this method of in situ scale-up would be the successful control of cellular growth within the engineered construct after engraftment,” they wrote. Since liver growth is known to be regulated by soluble growth factors (GFs), Stoddard screened a collection of candidate factors to identify those that, when added to cultured human primary hepatocyte cells (HEPs), had the strongest growth-inducing effects.
The genetic “BOOST” strategy integrates tissue engineering and synthetic biology tools to enable on-demand liver growth inside the body. By specifically rewiring the gene expression of primary liver hepatocytes and supportive fibroblast cells, a tissue growth program is switched on in a small, engineered liver construct after its implantation into recipients and upon addition of an inducing agent (shown as a pill). As a result, the hepatocytes in the construct start and continue to proliferate until a desired construct size has been reached and the inducing signal is not provided anymore. In mice, BOOST resulted in robust and healthy liver growth. [Wyss Institute at Harvard University]
“We ended up with a set of four growth factors, HGF, TGFa, WNT2 and RSPO3, that potently induced sparsely scattered HEPs to grow in the culture dish,” said Stoddard. “But when we tested whether they could do the same in 3D liver tissues consisting of densely packed HEPs and fibroblasts, they turned out to be ineffective. This led us to hypothesize that there must be an additional mechanism at work in human HEPs that inhibits cell proliferation in high-density conditions.”
The team homed in on a protein, YAP, that senses mechanical signals, and which was known to move from cells’ cytosol to their nucleus in low-density conditions to help express genes involved in cell proliferation. However, in high-density conditions when cells are compressed, YAP is degraded in the cytosol, which prevents the activation of those target genes and restricts proliferation.
“Importantly, when we overexpressed a non-degradable version of YAP in HEPs, which also reaches the nucleus in high-density conditions to partake in gene regulation, we successfully overrode this density checkpoint in HEPs,” Stoddard said. “Interestingly, we found that HEPs needed to be stimulated with both YAP and GFs in order to grow in densely packed 3D liver tissues.”
Toward the goal of safely inducing and controlling HEP proliferation in a living organism, and eventually human patients, the researchers deployed synthetic biology tools to locally install control of these signaling pathways in HEPs and fibroblast cells within the engineered 3D liver tissues themselves. “We set out to engineer a synthetic biology toolkit capable of locally modulating growth factor and YAP signaling within engineered liver tissue, enabling on-demand control of proliferation even after implantation,” they noted.
The team engineered fibroblast cell lines that each secreted one of the four GFs, and HEPs that expressed the non-degradable YAP protein. And they made the expression of all proteins doxycycline (DOX)-inducible. They determined in time course experiments that a continuous seven-day treatment with DOX led 3D liver tissue composed of engineered cells to robustly expand in size and cell numbers in the culture dish. On DOX removal the HEPs reverted back to a non-proliferating state.
However, Stoddard noted, “… when we compared the gene expression of single cells in BOOST-engineered, DOX-induced 3D liver tissue to that of cells in non-engineered or BOOST-engineered, non-induced 3D liver tissue, we noticed that the expansion came with a trade-off: high proliferation rates went hand in hand with a less functional HEP state. While we believe this is a natural trade-off seen in a wide variety of biological settings, we hope to be able to address this in the future, recognizing that the liver also has native re-functionalization signals to harness.”
The litmus test for BOOST-engineered growth in 3D liver tissues was to see whether they would similarly expand following their implantation into living mice that were systemically treated with DOX for the same seven-day duration. Experiments showed that the implanted tissue exhibited a striking 500% increase in proliferation with a doubling of the engineered HEPs alone, and was vascularized to accommodate the metabolic demands of the expanded tissue. The tissue implants were also well tolerated by the mice, with no signs of fibrosis due to invading immune cells and fibroblast inflammation, or of tumor growth.
“These results were particularly exciting to us,” said Stoddard. “Prior to our work, injury to the host liver has always been required to trigger hepatocyte engraftment and proliferation. Here we were able to relieve this dependence, and trigger on-demand growth of implanted liver tissue in a completely healthy host.”
In the future, the team will explore the capacity of BOOSTed liver tissue to rescue the host in the setting of liver injury. “Our BOOST strategy lays the foundation for a future when solid organ cell therapies can be controlled non-surgically according to the needs of patients and their physicians,” Bhatia noted. “Beyond treating liver disease, the premise of BOOST could be applied to other engineered tissue therapeutics that are similarly constrained by challenges associated with tissue scale-up, such as engineered heart or pancreatic tissue to address serious diseases.”
In their paper the authors concluded, “… this work serves as an exciting proof-of-concept demonstration that scale-up of tissues via growth could be possible … Together, this work helps lay the foundations for a future of ‘smart’ tissue therapeutics that can be scaled to a patient’s needs and thereby offer treatment for numerous, previously incurable, diseases.”
Background: Access to mental health care is critical for the effective management of serious mental illness (SMI), but consumers with low socioeconomic status (SES) have lower rates of service usage and worse retention in care. Digital technologies are often lauded as a way to bridge access gaps; however, little is known about how technology-mediated care may influence care access among low-SES consumers and how consumers use technology in care access. Objective: This study aimed to examine the applicability of Levesque et al’s access framework to technology-mediated care for SMI and analyze how low-SES consumers use technology to facilitate care access. Furthermore, the study assesses whether and how technologies are involved in care access at multiple points within the process of accessing care. Methods: This study used 2 qualitative methods: ethnographic observations at a mental health treatment court and interviews with low-SES consumers with SMI using community mental health care (n=14) and key informant interviews with health and service providers working with this population (n=14). Observations occurred from July 2022 through September 2023, and interviews occurred between January 2022 and May 2024. Data analysis involved both inductive and deductive coding approaches. Data from both the interviews and observations were analyzed in NVivo and further triangulated through analytic memos. Results: Levesque et al’s framework required several extensions to accommodate technology-mediated care related to SMI for low-SES consumers: (1) a cyclical rather than linear trajectory; (2) simultaneous care acquisition from multiple health and service providers; (3) staying in care long-term; (4) identification of both one-time and ongoing health needs; and (5) an emergency pathway for entering care. Consumers often faced challenges related to the varied digital requirements of each provider and a dearth of integrative, patient-facing tools like portals. Within this context, some consumers use mobile apps, communication, and telehealth technologies across various care access stages. Consumers used technology by figuring out how to navigate technology-mediated care, especially by leaning on others, such as case managers, for support. These others provided consumers with temporary technologies, showed them how to use technologies, and accompanied them through the process of using technology for accessing care. Conclusions: This study highlights that accessing care is iterative and ongoing, involving multiple forms of co-occurring service provision. A theoretical contribution of this work is its extension of Levesque et al’s care access framework to better reflect technology-mediated care for SMI among low-SES consumers. This work also underscores ongoing challenges for accessing technology-mediated care and the importance of human support in addressing access difficulties. Clinical implications include incorporating digital readiness assessments and providing comprehensive guidance on how consumers can effectively use technologies for care. Future work should investigate how technology-mediated care can make care access easier rather than harder.
<img src="https://jmir-production.s3.us-east-2.amazonaws.com/thumbs/3bc9f2d9db524662cf334a20a468cf05" />
<strong>Background:</strong> Effective communication about the relative risks of cigarettes and e-cigarettes can help increase switching away from cigarettes while minimizing unintended use. <strong>Objective:</strong> This study examined comprehension of a proposed modified exposure claim (MEC) about an e-cigarette (IQOS VEEV, the study product [SP]) and the effects of claim exposure on SP use intentions and risk perceptions among adult tobacco users and nonusers. <strong>Methods:</strong> Adult smokers with no intention to quit smoking (S-NIQ, n=606), adult smokers with an intention to quit smoking (S-IQ, n=600), adult e-cigarette users (ECU, n=630), adult former smokers (FS, n=619), adult tobacco and nicotine products (TNP) never-users aged 18-24 years (n=648), and adult TNP never-users aged 25 years and older (n=749; total N=3852) participated in a randomized between-groups online experimental study. Participants viewed a marketing brochure for the SP with (test condition) or without (control condition) an embedded MEC. Outcome measures included claim comprehension, intention to use the SP regularly, and perceived health risk to self from using the SP or smoking cigarettes. <strong>Results:</strong> Most participants were female (n=2110, 54.8%), had a mean age of 40.2 (SD 14.93) years, and were equally split across the 4 US regions. S-IQ and S-NIQ were long-term, frequent cigarette smokers, while 91.4% (566/619) of FS were long-term quitters. ECU on average used e-cigarettes ≥15.2 times per day, and the majority of them (552/630, 87.6%) had started using e-cigarettes more than 12 months before. Most participants correctly understood the key elements of the claim: the SP produces lower levels of harmful chemicals compared to cigarettes (1818/1926, 94.4%), and switching completely from cigarettes to the SP reduces exposure to harmful chemicals (1832/1926, 95.1%). In both conditions, positive intention to use the SP was high among ECU (control: 238/314, 75.8% vs test: 249/315, 79%; <i>P</i>=.33), moderate among S-IQ (control: 127/299, 42.5%; test: 166/299, 55.5%; <i>P</i><.001) and S-NIQ (control: 140/299, 46.8%; test: 166/307, 54.1%; <i>P</i>=.07), low among FS (control: 28/306, 9.2%; test: 33/312, 10.6%; <i>P</i>=.55), and very low among adult TNP never-users aged 18-24 years (control: 3/330, 0.9%; test: 8/318, 2.5%; <i>P</i>=.11), and adult TNP never-users aged 25 years and older (control: 5/373, 1.3% vs test: 12/375, 3.2%; <i>P</i>=.09). All groups understood that the SP posed a lower health risk compared to cigarettes. In all groups, claim exposure was associated with significantly lower risk perception of the SP relative to cigarettes (all comparisons, <i>P</i><.001). <strong>Conclusions:</strong> The tested MEC has the potential to benefit public health by simultaneously increasing already high levels of SP use intention and reducing SP risk perceptions relative to cigarettes among adult tobacco users while generating low levels of use intention among tobacco nonusers. <strong>Trial Registration:</strong>
<strong>Background:</strong> Campus shootings, though infrequent, result in significant loss of life, psychological trauma, and disruption to university communities. Traditional preparedness programs developed for K-12 settings do not translate well to university environments. Virtual reality (VR) offers an immersive and engaging method to enhance situational awareness and decision-making during high-stress events. <strong>Objective:</strong> This study aimed to develop the Safe@Campus prototype, a theory-informed, stakeholder-engaged VR-based prototype designed to prepare university students to recognize and respond to campus shooting threats, and to evaluate its initial usability and feasibility among undergraduate students. <strong>Methods:</strong> We followed a 2-phase, user-centered design process. Phase I (stakeholder-informed feasibility assessment and prototype refinement): through interviews with campus safety experts, firearm safety practitioners, school safety specialists, and students, we identified key content, scenario requirements, and implementation considerations. A 360-degree video–based VR prototype depicting an active shooter incident in a university classroom was developed using Unity3D, incorporating branching decision points aligned with the “run, hide, or fight” framework. Expert and user feedback guided iterative refinements. Phase II (student usability and acceptability testing): 2 focus groups with undergraduates at The Ohio State University (N=17) viewed a VR scenario and then participated in guided discussions about prior training experiences, the acceptability of VR, and recommendations for improvement. Transcripts were analyzed using constant comparative methods in ATLAS.ti (version 25). <strong>Results:</strong> The first focus group comprised 8 students (n=5, 63% female; n=3, 38% White, n=4, 50% Asian/Asian American), and the second comprised 9 students (n=6, 67% female; n=6, 67% White). Across both groups, 82% (14/17) reported participating in active shooter drills during K-12 schooling, yet many felt these experiences did not adequately prepare them for the complexity of university environments. The following four major themes emerged: (1) prior experience with active shooter drills: K-12 drills varied widely in realism and left students uncertain about appropriate actions in university settings; (2) need for university-specific training: participants noted substantial gaps in preparedness and expressed strong support for required, standardized training; (3) perceived usefulness of VR: students found VR highly engaging, realistic, and effective for reinforcing situational awareness and decision-making; and (4) recommendations for prototype improvement: students suggested increasing interactivity, adding time-pressured decisions, expanding scenarios to diverse campus spaces, and integrating the program into required university activities such as orientation. <strong>Conclusions:</strong> Safe@Campus is a feasible, acceptable, and engaging VR-based approach to campus shooting preparedness. Students viewed the immersive, decision-driven format as an effective way to build practical skills not addressed by traditional training. Future development should expand scenario diversity, increase interactivity, and evaluate program effectiveness in larger trials. <strong>Trial Registration:</strong>
SAN DIEGO — Alison Cameron spent close to a decade fighting to keep her myeloma under control. She’d been diagnosed with smoldering multiple myeloma, a precursor to cancer, and received infusions to keep it from progressing to active multiple myeloma for years. Now, after receiving CAR-T therapy, an aggressive immunotherapy, while on a trial, the 54-year old anesthesiologist is hoping the risk of cancer is gone for good.
It’s a reasonable hope, given the results of that trial, which researchers presented at the American Association for Cancer Research meeting here on Monday. All 20 patients who received the trial treatment no longer had any detectable myeloma cells in their body. That’s a far deeper and more complete response than scientists typically expect when it comes to multiple myeloma, and it’s prompting some experts to consider the possibility these patients have truly had active cancer permanently averted.
Currently, there is only one approved therapy for high risk smoldering myeloma, an antibody therapy called Darzalex. Patients can remain on treatment for years, but without achieving these kinds of deep molecular responses, and many still progress within five years, said Ecaterina Dumbrava, a cancer researcher at MD Anderson Cancer Center who did not work on the study. “The results raise a very important question: Whether early immune interception can not only delay progression but redefine treatment goals? Can we talk about the word we always avoid, which is cure?” she said.
Researchers at Penn State University have developed a method to create 3D-printed soft electrodes that can conform to an individual brain surface to provide more accurate patient-specific tracking of biophysical signals in the brain. The study, published in Advanced Materials, details a new technique to create neural interfaces that improve upon current stiff methods to more closely conform to the complex structure of the brain.
“Each person has a different brain structure, depending on their height, weight, age, sex and more,” said Tao Zhou, PhD, Wormley Family Early Career Professor and corresponding author of the study. “Despite this, we try to fit neural interfaces onto brains like they have identical structures. This motivated us to create electrodes that are tailored for each individual, based on the structure of their brain.”
The new electrodes are created using hydrogel, a water-rich material that has properties similar to brain tissue, and built in a honeycomb-like internal structure to help balance flexibility and strength. These soft electrodes, dubbed HiPGE for honeycomb-inspired printable gel electrodes, are fabricated using a 3-D printing method called direct ink writing, which allows for precise shaping at very small scales. The honeycomb design reduces stiffness allowing the electrodes to stretch and conform to the brain’s ridges and grooves without damaging brain tissue.
To individualize the design process, a patient would first have an MRI scan, which is used to create detailed simulations of each brain scanned. The simulations inform the how to create the shape of each electrode so it aligns with the patient’s specific cortical folds. The team then 3D prints both the electrode and a model of the brain to test how closely the device fits. In experiments involving 21 human brain models, the printed electrodes demonstrated improved conformity compared to traditional designs.
“The unique gyral patterns of the human brain demand patient-specific neural interfaces to achieve precise neuromodulation, mitigate adverse tissue responses, and optimize therapeutic efficacy and safety,” the researchers wrote, noting that conventional rigid electrodes “exhibit limited conformability to the brain’s heterogeneous cortical topography,” resulting in “poor electrode-tissue contact, signal loss, and foreign body responses.”
To evaluate HiPGE performance and biological compatibility, the researchers conducted 28-day in vivo tests in rat models. Results from the tests showed that electrodes maintained stable function for the entire the testing period and did not trigger an immune response. The flexible electrodes also provided consistent and accurate readings of electrical and physiological signals in the brain.
Prior research has studied soft-material neural interfaces, but customization to individual gyral patterns has been limited. The introduction of a combined imaging, modeling and printing design workflow has solved this limitation by enabling electrodes to be tailored at the patient level.
The researchers wrote that the folded structure of the brain “creates a unique ‘fingerprint’ for each brain.” They also noted that current rigid devices can lead to “signal degradation due to scar formation,” and can create instability caused by the mismatch between the stiff neural interface materials and soft brain tissue.
Clinically, the improved contact between electrode and brain tissue could provide more reliable monitoring of neural activity, an important improvement for diagnosing and managing neurological conditions. Better signal fidelity could enhance applications such as brain-computer interfaces, neuroprosthetics, and neuromodulation therapies. The soft, conformable design may also reduce complications associated with long-term implantation, including inflammation and tissue damage.
“This tailored design ensures robust electrode-tissue integration, minimizing mechanical mismatch and improving signal fidelity during in vivo neural activity recording,” the researchers wrote. They added that studies “confirmed HiPGE’s biocompatibility, revealing no significant immune response or structural disruption to brain tissue.”
Future research will seek refine the technology for specific disease monitoring and exploring its use in clinical settings. They also aim to optimize the devices for targeted neurological conditions, which could inform the development of more precise and individualized care strategies.
Chimeric antigen receptor (CAR) T cell therapies have transformed the treatment of certain blood cancers, yet translating this success to solid tumors has remained a major challenge. One of the key obstacles has been T cell exhaustion, a state in which engineered immune cells lose their ability to sustain an effective anti-tumor response.
Now, early clinical data from a first-in-human Phase I trial suggest a new approach may help overcome this limitation. Presenting at the AACR annual meeting in San Diego, researchers from the Perelman School of Medicine at the University of Pennsylvania report that a novel “KIR-CAR” T cell therapy shows promising safety and early efficacy signals across multiple solid tumor types.
New design inspired by natural killer cells
The investigational therapy, SynKIR-110, represents a departure from traditional CAR T designs. Rather than using a single-chain receptor, the therapy is modeled after natural killer (NK) cell receptors and uses a “multi-chain” architecture.
This design separates tumor recognition from activation, effectively creating an intrinsic “on-off” mechanism. The T cell remains in a resting state until it encounters its target, at which point the receptor components assemble to trigger an immune attack.
“The KIR-CAR design provides a natural ‘on-off’ mechanism, which helps avoid the problem of T cell exhaustion,” said Janos L. Tanyi, MD, PhD, principal investigator of the study. “The CAR turns on when it finds its target, kills it, and then rests, rather than constantly burning energy.”
This contrasts with conventional CAR T cells, which remain continuously active and can become depleted over time, limiting their effectiveness—particularly in the more complex microenvironment of solid tumors.
Early clinical signals in difficult-to-treat cancers
The Phase I dose-escalation trial enrolled nine patients with advanced, mesothelin-expressing cancers, including ovarian cancer, mesothelioma, and cholangiocarcinoma. These patients had limited treatment options, having received an average of four prior lines of therapy.
Although the primary goal of the study was to assess safety, early signs of efficacy were observed. Disease stabilization was reported in four patients, and one patient in the highest dose cohort achieved an ongoing partial response.
“These are cancer types that have never had an approved cell therapy,” Tanyi said. “We’re seeing good efficacy signals, even at low doses, and limited toxicity.”
The results suggest that the therapy may be able to generate meaningful anti-tumor responses even in heavily pretreated populations.
Favorable safety profile
Safety has been another major barrier for CAR T therapies, particularly in solid tumors. However, the KIR-CAR approach appears to mitigate some of these concerns.
No dose-limiting toxicities were observed in the initial cohorts. Cytokine release syndrome (CRS), a common side effect of CAR T therapy, occurred in 33% of patients but was limited to low-grade events. Notably, there were no cases of immune effector cell-associated neurotoxicity syndrome (ICANS), a more severe complication sometimes seen with CAR T therapies.
The ability to limit toxicity while maintaining activity is a key step toward broader application of cell therapies in solid tumors.
Targeting mesothelin across tumor types
SynKIR-110 targets mesothelin, a protein expressed on the surface of several solid tumors but largely absent from normal tissues. This makes it an attractive target for immunotherapy, particularly in cancers such as ovarian cancer and mesothelioma, where treatment options are limited.
The trial results indicate that the therapy’s activity is not confined to a single tumor type, raising the possibility of broader applicability across mesothelin-expressing cancers.
Expanding CAR T into solid tumors
The findings come amid growing efforts to adapt CAR T technology for solid tumors. While the approach has revolutionized hematologic malignancies, solid tumors present additional challenges, including immunosuppressive microenvironments, physical barriers to T cell infiltration, and antigen heterogeneity.
Researchers are exploring multiple strategies to address these barriers, including improved targeting, combination therapies, and next-generation receptor designs such as KIR-CAR.
As noted by CAR T pioneer Carl June, MD, advancing cellular therapies into solid tumors remains a central goal for the field.
Looking ahead
The Phase I study is ongoing, with plans to enroll up to 42 patients and identify the maximum tolerated dose before advancing to a Phase II trial. Early data indicate that CAR T cell expansion in the blood increases with dose, suggesting that higher doses may further enhance efficacy.
While still preliminary, the results highlight the potential of multi-chain CAR designs to address one of the most persistent challenges in cell therapy: maintaining durable activity without excessive toxicity.
If confirmed in larger studies, KIR-CAR therapies could represent a new generation of engineered immune cells, ones that more closely mimic natural immune regulation while retaining the precision of targeted cancer therapy.
For now, the data offer an encouraging signal that the next wave of CAR T innovation may finally extend the reach of cell therapy into solid tumors, where the need remains greatest.
![The genetic “BOOST” strategy integrates tissue engineering and synthetic biology tools to enable on-demand liver growth inside the body. By specifically rewiring the gene expression of primary liver hepatocytes and supportive fibroblast cells, a tissue growth program is switched on in a small, engineered liver construct after its implantation into recipients and upon addition of an inducing agent (shown as a pill). As a result, the hepatocytes in the construct start and continue to proliferate until a desired construct size has been reached and the inducing signal is not provided anymore. In mice, BOOST resulted in robust and healthy liver growth. [Wyss Institute at Harvard University]](https://www.genengnews.com/wp-content/uploads/2026/04/Low-Res_Press-graphics-01-300x225.jpg)
