Centre Hospitalier Universitaire Vaudois

The body’s “killer” T cells don’t just attack—they strike with astonishing precision, forming a tiny, highly organized contact zone that lets them destroy dangerous cells without harming their neighbors. Now, scientists have captured this process in unprecedented detail, revealing a hidden world of molecular choreography.Cytotoxic T lymphocytes act as the immune system's specialized "killer" cells, seeking out and eliminating infected or cancerous cells with remarkable precision. Their effectiveness depends on a tightly controlled contact point called the "immune synapse," where they release toxic molecules that destroy the target while leaving surrounding healthy cells unharmed. Until recently, scientists struggled to observe the fine structure of this process in detail. Now, researchers from the University of Geneva (UNIGE) and the Lausanne University Hospital (CHUV) have managed to visualize these mechanisms in three dimensions under near-native conditions. Their findings, published in Cell Reports, shed new light on how the internal organization of cytotoxic T cells supports their function and could advance research in immuno-oncology. When the body faces infection or cancer, cytotoxic T lymphocytes bind tightly to their target and form the immune synapse. Through this specialized interface, they release toxic substances that trigger the destruction of the harmful cell. This targeted approach allows the immune system to remove threats efficiently while minimizing collateral damage to nearby tissue. Although scientists have long understood the basics of this process, studying its detailed structure at the nanometer scale inside intact human cells has remained challenging. A major difficulty comes from how samples are prepared, since traditional methods can distort delicate cellular components. Existing imaging techniques often force researchers to choose between high resolution, a large field of view, or preserving the cell's natural structure. Cryo-Expansion Microscopy Reveals Hidden Details To overcome these challenges, the UNIGE and CHUV-UNIL team, supported by the ISREC Foundation TANDEM program, used an advanced method called cryo-expansion microscopy (cryo-ExM). "This technique involves instantaneously freezing cells at very high speed, placing them in a so-called vitreous state, where water solidifies without forming crystals and thus faithfully preserves biological structures. The samples are then physically expanded using an absorbent hydrogel, making it possible to observe their internal organization with great precision while maintaining their near-native architecture," explains Virginie Hamel, Senior Lecturer in the Department of Molecular and Cellular Biology at the Faculty of Science of UNIGE. Using this approach, the researchers uncovered new structural features at the point where the immune cell meets its target. "Our work reveals that at the point of contact between the immune cell and its target, the membrane forms a kind of dome, whose structure appears to be linked to adhesion interactions and to the internal organization of the cell," notes Florent Lemaître, postdoctoral researcher in the Department of Molecular and Cellular Biology at the Faculty of Science of UNIGE and first author of the study. The team also examined cytotoxic granules, which are responsible for killing target cells, with unprecedented clarity. They found that these granules can differ in structure, sometimes containing one or multiple "cores" where the active molecules are concentrated. From Laboratory Cells to Real Tumors The researchers extended their method beyond isolated cells and applied it directly to human tumor samples. "We extended this approach to human tumor tissues, making it possible to directly observe T lymphocytes infiltrating tumors and their cytotoxic machinery at the nanometer scale. This allows us to study immune responses directly in their clinical context and to better understand the mechanisms that determine their effectiveness," explains Benita Wolf, Chief Resident and Associate Researcher in the Department of Clinical Oncology at CHUV, who co-led the study. By providing a three-dimensional and near-native view of how these immune cells operate, the work offers a valuable framework for studying immune responses in real-world conditions. These insights could help refine treatments, especially in immuno-oncology, by improving our understanding of what drives successful immune attacks against cancer and what limits them.

Investigational ARC-BCI ® Therapy is being developed to restore thought-driven movement in people living with spinal cord injuries and other movement disabilities ARC-BCI is the world’s first and most advanced purpose-designed platform pairing a brain-computer interface with an implantable spinal cord stimulation system Seven study participants have now received ARC-BCI Therapy to restore movement of their own paralyzed limbs EINDHOVEN, the Netherlands, Jan. 22, 2026 (GLOBE NEWSWIRE) -- ONWARD Medical N.V. (Euronext: ONWD – US ADR: ONWRY), the neurotechnology company pioneering spinal cord stimulation therapies to restore movement, function, and independence, announces that two additional individuals living with spinal cord injuries (SCI) have received the Company’s investigational ARC-BCI ® Therapy. These groundbreaking procedures bring the total number of human implants to seven, extending the Company’s leadership in the development of brain-computer interface (BCI) platforms to restore thought-driven movement for people living with paralysis. Both procedures were performed at the Centre Hospitalier Universitaire Vaudois (CHUV) in Lausanne, Switzerland, under the direction of Jocelyne Bloch, MD, Chief of Neurosurgery. They involved a 35-year-old woman who sustained a spinal cord injury two years ago and a 39-year-old man who sustained a spinal cord injury seven years ago. Study participants received ARC-BCI Therapy for upper- and lower-limb movement restoration, respectively. “We continue to learn from this groundbreaking clinical feasibility research, leveraging our unique understanding of spinal cord stimulation to restore movement after paralysis, and exploring the potential advantages offered by the addition of a brain-computer interface,” said Dave Marver, CEO of ONWARD Medical. “We look forward to sharing more details in a peer-reviewed forum, continuing our commitment to scientific rigor.” The Company’s BCI platform comprises an implant placed epidurally on the motor cortex, designed to record brain signals associated with movement intention. The system uses Artificial Intelligence (AI) to decode these signals and translate them into instructions that are wirelessly transmitted to an implanted neurostimulator, which precisely stimulates targeted regions of the spinal cord via purpose-designed leads. The Company’s BCI is supported by more than eight years of human safety data. The ARC-BCI System was awarded Breakthrough Device Designation (BDD) by the US Food and Drug Administration (FDA) in 2024. ARC-BCI is also included in the FDA’s Total Product Life Cycle Advisory Program that provides early regulatory guidance to support the development of innovative technologies. These latest implants are part of ongoing clinical feasibility studies supported by grants from the European Union’s Horizon Europe research and innovation program through the European Innovation Council (EIC, under grant agreements No 101057450 and 101070891), the Christopher & Dana Reeve Foundation, and the Swiss State Secretariat for Education, Research and Innovation (SERI). About ONWARD Medical ONWARD Medical is the leading neurotechnology company pioneering therapies to restore movement, function, and independence in people with spinal cord injuries (SCI) and other movement disabilities. Building on decades of scientific discovery, preclinical research, and clinical studies conducted at leading hospitals, rehabilitation clinics, and neuroscience laboratories, the Company developed its proprietary ARC Therapy. It has subsequently been awarded 10 Breakthrough Device Designations from the FDA. The Company’s ARC EX ® System is cleared for commercial sale in the US and Europe. The Company is also developing an investigational implantable system called ARC-IM ® , designed to address several unmet needs including blood pressure instability after spinal cord injury. It can also be paired with a brain-computer interface (BCI) and artificial intelligence (AI) to restore thought-driven movement. Headquartered in the Netherlands, the Company has a Science and Engineering Center in Switzerland and a US office in Boston, Massachusetts. The Company is listed on Euronext Paris, Brussels, and Amsterdam (ticker: ONWD) and its US ADRs can be traded on OTCQX (ticker: ONWRY). To learn more about ONWARD Medical’s commitment to partnering with the spinal cord injury community to develop innovative solutions for restoring movement, function, and independence after spinal cord injury, please visit ONWD.com . To be kept informed about the Company’s technologies, research studies, and the availability of therapies in your area, please complete this webform . For Media Inquiries: Sébastien Cros, VP Communications media@onwd.com For Investor Inquiries: investors@onwd.com Disclaimer Certain statements, beliefs, and opinions in this press release are forward-looking, which reflect the Company’s or, as appropriate, the Company directors’ current expectations and projections about future events. By their nature, forward-looking statements involve several risks, uncertainties, and assumptions that could cause actual results or events to differ materially from those expressed or implied by the forward-looking statements. These risks, uncertainties, and assumptions could adversely affect the outcome and financial effects of the plans and events described herein. A multitude of factors including, but not limited to, delays in regulatory approvals, changes in demand, competition, and technology, can cause actual events, performance, or results to differ significantly from any anticipated development. Forward-looking statements contained in this press release regarding past trends or activities should not be taken as a representation that such trends or activities will continue in the future. As a result, the Company expressly disclaims any obligation or undertaking to release any update or revisions to any forward-looking statements in this press release as a result of any change in expectations or any change in events, conditions, assumptions, or circumstances on which these forward-looking statements are based. Neither the Company nor its advisers or representatives nor any of its subsidiary undertakings or any such person’s officers or employees guarantees that the assumptions underlying such forward-looking statements are free from errors nor does either accept any responsibility for the future accuracy of the forward-looking statements contained in this press release or the actual occurrence of the forecasted developments. You should not place undue reliance on forward-looking statements, which speak only as of the date of this press release. Trademarks: ONWARD, ARC-EX, ARC-IM, ARC-BCI, and the stylized O-Logo are proprietary and registered trademarks of ONWARD Medical. Unauthorized use is strictly prohibited. ARC-EX Indication for Use: The ARC-EX System is intended to deliver programmed, transcutaneous electrical spinal cord stimulation in conjunction with functional task practice in the clinic and with take-home exercises in the home to improve hand sensation and strength in individuals between 18 and 75 years old that present with a chronic, nonprogressive neurological deficits resulting from an incomplete spinal cord injury (C2-C8 inclusive). The ARC-EX System is intended to be operated in medical centers by rehabilitation professionals and at home by patients and persons providing assistance to patients, as needed. Other Investigational Products: All other ONWARD Medical devices and therapies including ARC-IM and ARC-BCI are investigational and not available for commercial use .

PRESS RELEASE Results from a Phase I clinical trial of a dendritic cell targeting prophylactic HIV vaccine published in the Journal eClinical Medicine Provides important validation of the safety and immunogenicity of EnnoDC’s technology The ANRS VRI06 trial, carried out by Inserm, ANRS MIE and the VRI, shows that the CD40.HIVRI.Env vaccine, is safe and induces early and sustained humoral and cellular immune responses against HIVThe first clinical trial results in humans with this novel type of vaccine, which consists of a monoclonal antibody fused to the HIV envelope, targeting the CD40 molecule expressed at the surface of dendritic cellsResults were published in the Journal eClinical Medicine, an open access clinical journal, published by The Lancet Paris, France, 2 October 2024 – EnnoDC* (or “the Company”), a clinical-stage biotech company pioneering the development of first-in-class dendritic cell-targeting immunotherapies, today notes the publication of positive results from a Phase I trial of its novel Dendritic Cell (DC) targeting prophylactic HIV vaccine in the Journal eClinical Medicine, an open access clinical journal, published by The Lancet. The multicentre, double-blind placebo-controlled dose-escalation trial was conducted at clinical sites in France and Switzerland. The results, published by scientists from the Vaccine Research Institute of Inserm and the Université Paris-Est Créteil, the CHUV in Lausanne and the University of Bordeaux, show that the vaccine, CD40.HIVRI.Env, is safe and induces early and sustained humoral and cellular immune responses against HIV. No serious side effects were observed. General and local reactions at the injection site were mainly mild to moderate. Two severe adverse events were reported, which were found to be unrelated to vaccination after analysis. EnnoDC’s first-in-class approach combines the power of vaccines and immunotherapies to provide targeted immune responses for both cancer and infectious diseases. CD40.HIVRI.Env combines a humanized anti-CD40 monoclonal antibody fused with HIV envelope antigens to stimulate DCs through CD40 and deliver a targeted immune response. Pr. Yves Lévy, co-founder, Chief Medical and Scientific Officer at EnnoDC and Principal Investigator of the trial commented: “These are exciting results for EnnoDC from the first clinical study using our novel dendritic cell targeting technology. The results show that this vaccine is safe and well tolerated and that humoral and cellular immune response were activated against HIV. The results support further development of the program. In addition, the results show that this type of treatment, which specifically targets antigens to the dendritic cells via the CD40 molecule, may be potent in inducing protective immunological responses in prime-boost vaccination strategies.” Christophe Hubert, Chief Executive Officer of EnnoDC, added: “These are very encouraging results which provide further validation of our technology with positive read across to our new immunotherapies, in development for HPV-induced cancers, prostate cancer and infectious diseases.” Last week EnnoDC unveiled the next generation of DC-targeting immunotherapies supported by new leadership and an evolved strategy. EnnoDC has an extensive pipeline of clinical and preclinical stage assets in HPV-induced cancers, prostate cancer and in infectious diseases. Further information on the ANRS VRI06 trial is available in a press release issued by the Vaccine Research Institute (VRI) of Inserm and the Université Paris-Est Créteil (Unit 955 Mondor Institute for biomedical research), the CHUV in Lausanne and the University of Bordeaux through the link below:Preventive vaccine against HIV: promising results in healthy volunteers with a new vaccine technology – Vaccine Research Institute (vaccine-research-institute.fr) The full paper, published in the October 2024 issue of eClinical Medicine, can be accessed through the following link: https://doi.org/10.1016/j.eclinm.2024.102845. Further details about the trial can be found online at https://clinicaltrials.gov/study/NCT04842682. *EnnoDC is the trading name of LinKinVax Europe SAS. -Ends- For more information please contact: EnnoDC Christophe Hubert, CEOinfo@EnnoDC.com ICR Consilium Ashley Tapp / Jonathan Edwards / Kumail Waljee EnnoDC@consilium-comms.comTel: +44 (0) 20 3709 5700 About EnnoDC EnnoDC, the trading name of LinKinVax, is a clinical-stage biotech company pioneering the development of first-in-class Dendritic Cell (DC)-targeting immunotherapies. Through our versatile DC-targeting immunotherapy platform we are developing CD40-specific monoclonal antibodies fused with pathogenic antigens to induce a highly specific, safe, broad, and long-lasting immune response to combat diseases like cancer and infectious diseases. The Company currently has three active clinical trials in various stages of clinical development, addressing oncology and infectious disease indications. Its lead asset, CD40HVac is currently in a Phase I/IIa clinical trial for HPV16+ oropharyngeal cancer patients. EnnoDC is a spin out from the Vaccine Research Institute (VRI), an institute of INSERM (the French National Institute of Health and Medical Research) and is supported by longstanding investors and internationally renowned key opinion leaders who contribute their expertise in the clinical development of EnnoDC’s assets and help explore the expansive therapeutic potential of its innovative platform. Find out more online at: http://www.EnnoDC.com Follow us on X and LinkedIn About ANRS MIEANRS Emerging Infectious Diseases is an autonomous agency of Inserm (the French National Institute for Health and Medical Research). Its mission is to facilitate, evaluate, coordinate and fund research into HIV/AIDS, viral hepatitis, sexually transmitted infections, tuberculosis and emerging and re-emerging infectious diseases. For more information: https://anrs.fr/en/ About the VRI and Inserm The Vaccine Research Institute (VRI), Laboratory of excellence, was established by Inserm (French National Institute of Health and Medical Research) and the University of Paris-Est Créteil (UPEC) to conduct research to accelerate the development of effective vaccines against HIV/AIDS and (re)-emerging infectious diseases. The VRI's structure strengthens the links between basic research and translational research, patient associations and the socio-economic world. The VRI extends a network of internationally renowned scientists and research teams with multidisciplinary expertise in system biology and clinical immunology, a network of clinical centres, and shared platform.For more information: https://vaccine-research-institute.fr/ Founded in 1964, Inserm is a public scientific and technological institute dedicated to biomedical research and human health and is involved in the entire range of activities from the laboratory to the patient’s bedside. It also partners with the most prestigious research institutions in the world that are committed to scientific challenges and progress in these fields.For more information: https://www.inserm.fr/en/home/ About Université Paris-Est Créteil: With 14 faculties, schools and institutes, 1 observatory and 32 research laboratories, Université Paris-Est Créteil has been active in all fields of knowledge since 1970. Each year, UPEC trains over 42,000 students and working professionals of all ages. A major player in the dissemination of academic, scientific and technological knowledge, the university offers more than 500 training courses in all disciplines and at all levels. UPEC offers personalized support for all successes, thanks to undergraduate and graduate training, recognition of prior learning and lifelong learning opportunities. Furthermore, the university runs a growing number of apprenticeship programs in order to stimulate entrepreneurship and ease professional integration. Université Paris-Est Créteil has built its strategic plan around three strategic orientations: UPEC is an engaged university that aims to match academic excellence with societal relevance. It encourages and supports all paths of students’ success with dedicated programs. UPEC masters its trajectory and is a university open to the world and its diversity. For more information: https://www.en.u-pec.fr/ About the University of Bordeaux With more 54,000 students, 3,200 researchers and teachers, and 2,800 staff members, the University of Bordeaux is one of the leading French public research and higher education institutions, located in a dynamic and culturally rich, fast-developing region. Ranked among the top universities in France, the University of Bordeaux is renowned for the quality of its academic courses and research. It is a multi-disciplinary, research-focused institution with a strong ambition to develop as a leading, international campus. The University of Bordeaux is leading an ambitious, competitive development program in partnership with local higher education institutes and national research organizations, in order to promote Bordeaux as a “Campus of Excellence”. For more information: https://www.inserm.fr/en/home/