In this Review, the authors discuss current strategies for in vivo CAR engineering of T cells and other immune cells and explore future directions and potential applications for the advancement of in vivo CAR engineering technologies.
- Chimeric antigen receptor (CAR)-engineered immune cell therapy represents an important advance in cancer treatments. However, the complex ex vivo cell manufacturing process and stringent patient selection criteria curtail its widespread use.
- In vivo CAR engineering is emerging as a promising off-the-shelf therapy, providing advantages such as streamlined production, elimination of patient-specific manufacturing, reduced costs and simplified logistics.
- Among the various approaches to in vivo CAR engineering, LNP–mRNA-based CARs have a strong chance of reaching the clinic first, leveraging the manufacturing and regulatory advancements established during the COVID-19 pandemic.
- Preclinical proof-of-concept studies in cancer and cardiac injury models have demonstrated functional equivalence between therapeutic cells that were engineered in vivo and those produced via conventional ex vivo methods.
- Before taking in vivo CAR engineering to the clinic, it is essential to conduct a comparative analysis across the various vector technologies to identify those that provide an optimal balance among efficacy, immunogenicity and safety.
- Patient selection for in vivo CAR engineering would be likely to prioritize individuals with relatively intact immune systems, as endogenous T cells must respond to the in vivo gene delivery, expand and persist for therapeutic efficacy. This could exclude heavily pretreated patients with profound lymphopenia or those with a highly immunosuppressive TME.
DIU Immunologie et Biotherapies is a french diploma associating french universities and immunology laboratories. It is dedicated to the involvement of immunology in new biotherapies, either molecular or cellular.
Gilbert C FAURE's insight:
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Thrilled to have attended last week’s virtual "𝙄𝙣 𝙑𝙞𝙫𝙤 𝙀𝙣𝙜𝙞𝙣𝙚𝙚𝙧𝙞𝙣𝙜 𝙤𝙛 𝙄𝙢𝙢𝙪𝙣𝙚 𝘾𝙚𝙡𝙡𝙨 (𝙄𝙑𝙀𝙄𝘾)" workshop hosted by the 𝗡𝗖𝗜! 🚀
𝘐𝘯 𝘷𝘪𝘷𝘰 cell engineering is redefining the possibilities of immunotherapy—offering the potential for 𝗳𝗮𝘀𝘁𝗲𝗿, 𝗺𝗼𝗿𝗲 𝗮𝗰𝗰𝗲𝘀𝘀𝗶𝗯𝗹𝗲, 𝗮𝗻𝗱 𝗹𝗲𝘀𝘀 𝗿𝗲𝘀𝗼𝘂𝗿𝗰𝗲-𝗶𝗻𝘁𝗲𝗻𝘀𝗶𝘃𝗲 treatments compared to traditional 𝘦𝘹 𝘷𝘪𝘷𝘰 approaches.
𝗦𝗼𝗺𝗲 𝗸𝗲𝘆 𝗮𝗱𝘃𝗮𝗻𝘁𝗮𝗴𝗲𝘀 𝗶𝗻𝗰𝗹𝘂𝗱𝗲: ✅ No need for GMP manufacturing facilities ✅ Shorter and more scalable workflows ✅ Potential for outpatient or point-of-care delivery
⚠️ 𝗕𝘂𝘁 𝗰𝗵𝗮𝗹𝗹𝗲𝗻𝗴𝗲𝘀 𝗿𝗲𝗺𝗮𝗶𝗻: - Reduced control over the engineering process - Difficulties in targeting specific immune subsets - Efficacy and safety still under active investigation
🔥 𝗬𝗲𝘁 𝘁𝗵𝗲 𝗺𝗼𝗺𝗲𝗻𝘁𝘂𝗺 𝗶𝘀 𝘂𝗻𝗱𝗲𝗻𝗶𝗮𝗯𝗹𝗲! 🔥
🌟 𝗦𝗼𝗺𝗲 𝗵𝗶𝗴𝗵𝗹𝗶𝗴𝗵𝘁𝘀:
- Carl June (University of Pennsylvania) laid the groundwork with a visionary keynote on 𝘦𝘹 𝘷𝘪𝘷𝘰 and 𝘪𝘯 𝘷𝘪𝘷𝘰 CAR-T.
- Matthias Stephan (WHI CCC Fred Hutchinson Cancer Research Center) showcased the power of local reprogramming via 𝘪𝘯 𝘷𝘪𝘷𝘰 engineering of macrophages to secrete BiTEs.
- Yevgeny Brudno (University of North Carolina at Chapel Hill Chapel Hill) introduced implantable sponges enabling same-day CAR T therapy.
- Cristiana Pires (Asgard Therapeutics) proposed turning tumors into antigen-presenting cells through 𝘪𝘯 𝘷𝘪𝘷𝘰 reprogramming.
- Daniel G. (Myeloid Therapeutics) shared early clinical data on 𝘪𝘯 𝘷𝘪𝘷𝘰 mRNA CAR myeloid engineering.
- Adrian Bot, M.D., Ph.D. (Capstan Therapeutics) presented Capstan’s LNP platform tackling both oncology and autoimmunity.
👏 Kudos to all the speakers and organizers for advancing this paradigm-shifting field.
The search for potent malaria vaccine candidate has seen several twists and turns. Here, we provide a perspective on the current state of PfRH5-based malaria vaccine development, the progress, existing challenges, and future research directions. We discuss the clinical trials in endemic regions, immune correlates of protection, prospects of integrating PfRH5 into multi-antigen vaccine strategies and considerations on the onward development/deployment of PfRH5 vaccine from the laboratory to endemic communities.
Beginning with Edward Jenner’s discovery of the smallpox vaccine, the ever-expanding repertoire of vaccines against pathogens has saved many lives. During the COVID-19 pandemic, a revolutionary mRNA injectable vaccine emerged that effectively controlled the severity of disease caused by SARS-CoV-2. This vaccine induced potent antigen-specific neutralizing serum IgG antibodies, but was limited in its ability to prevent viral invasion at the respiratory surfaces. Nasal vaccines have attracted attention as a potential strategy to combat respiratory infections and prepare for future pandemics. Input from disciplines such as microbiology, biomaterials, bioengineering and chemistry have complemented the immunology to create innovative delivery systems. This approach to vaccine delivery has yielded nasal vaccines that induce secretory IgA as well as serum IgG antibodies, which are expected to prevent pathogen invasion, thereby diminishing transmission and disease severity. For a nasal vaccine to be successful, the complexity of the relevant anatomical, physiological and immunological properties, including the proximity of the central nervous system to the nasal cavity, must be considered. In this Review, we discuss past and current efforts as well as future directions for developing safe and effective nasal vaccines for the prevention of respiratory infections. This Review provides an overview of progress and future directions in the development of nasally administered vaccines for respiratory infections.
The effectiveness of intramuscular vaccines aimed at preventing severe COVID-19 remains limited due to waning immunity and the emergence of novel variants. Next-generation vaccines are needed for broader protection and blocking virus transmission. Here, we rationally designed an original nasal subunit vaccine composed of a fusion protein (SwFN) made of Wuhan spike and nucleoprotein combined with biocompatible mucosal nanocarriers (Nc). In mouse model, the nasal Nc-SwFN vaccine elicited multivalent serum and mucosal neutralizing antibodies. Robust spike and nucleoprotein cross-reactive immunity against variants was induced with a predominant phenotype of resident memory T cells in the lungs. Moreover, Nc-SwFN led to protective responses against Wuhan and Delta infection in relevant models with an absence of morbidity, mortality, and virus dissemination in the lungs and brain. Finally, Nc-SwFN drastically reduced host-to-host transmission. These promising results underscore the advantages of the nasal Nc-SwFN approach as a broad-spectrum vaccine candidate against current and emerging SARS-CoV-2 variants.
BMJ Publishing Group. Pancreatic Cancer. https://bestpractice.bmj.com/topics/en-us/265 Updated November 19, 2024. Accessed March 19, 2025. Yu B, et al. Frontiers in pancreatic cancer on biomarkers, microenvironment, and immunotherapy. Cancer Lett. 2025;610:217350.
#highlyviewed 📢 An Update on Anti- #COVID19 #Vaccines and the Challenges to Protect Against New #SARSCoV2 Variants 👨🎓 by Fábio Mambelli et al. 🔗 Full article: mdpi.com/2076-0817/14/1/23
The COVID-19 pandemic has posed a significant threat to global health systems, with extensive impacts across many sectors of society. The pandemic has been responsible for millions of deaths worldwide since its first identification in late 2019. Several actions have been taken to prevent the disease, including the unprecedented fast development and global vaccination campaigns, which were pivotal in reducing symptoms and deaths. Given the impact of the pandemic, the continuous changes of the virus, and present vaccine technologies, this review analyzes how, so far, we have met the challenge posed by the emergence of new variants and discusses how next-generation pan-coronavirus vaccines, with enhanced longevity and breadth of immune responses, may be tackled with alternative administration routes and antigen delivery platforms. By addressing these critical aspects, this review aims to contribute to the ongoing efforts to achieve long-term control of COVID-19, stimulating the discussion and work on next-generation vaccines capable of facing future waves of infection.
Australia approves its first non-COVID mRNA vaccine, Moderna’s mresvia, for RSV in older adults. The U.S. FDA clears a freeze-dried Jynneos for mpox and smallpox, boosting biodefense readiness. Pfizer expands RSV vaccine Abrysvo use in Europe to at-risk adults. Desentum reports positive Phase 1 results for birch pollen allergy vaccine DM-101PX. NEC unveils a secure workflow for personalized cancer vaccine delivery. Novavax awaits FDA approval for its protein-based COVID-19 vaccine, offering a non-mRNA alternative backed by Phase 3 safety and efficacy data.
I'm pleased to share with you the first of two publications with Arti Rai on the legal and regulatory landscape around biologics manufacturing patents. Using…
The response to vaccination depends on many factors and is based on the 4 Ws: Who, When, What, and Where.
In this article, the authors, focusing on the last W (Where), sought to identify the determinants associated with a better response to booster vaccination when administered at the same site as the initial vaccination.
They were able to show that in mice Bmems in dLNs reside in a subcapsular niche rich in CD169+ macrophages (SSMs) that interact closely with these cells, promoting their re-entry into germinative centers (GCs) after booster vaccination. Bmems in ndLNs (non-draining LNs) are more dispersed, migrate deeper into the follicles, and preferentially differentiate into plasma cells rather than GC cells.
The study in the mouse model was supplemented by a study in humans comparing, as has been done in the past, ipsilateral versus contralateral booster vaccination with a COVID-19 mRNA vaccine, demonstrating the superiority of ipsilateral vaccination.
In this Review, the authors discuss current strategies for in vivo CAR engineering of T cells and other immune cells and explore future directions and potential applications for the advancement of in vivo CAR engineering technologies.
- Chimeric antigen receptor (CAR)-engineered immune cell therapy represents an important advance in cancer treatments. However, the complex ex vivo cell manufacturing process and stringent patient selection criteria curtail its widespread use.
- In vivo CAR engineering is emerging as a promising off-the-shelf therapy, providing advantages such as streamlined production, elimination of patient-specific manufacturing, reduced costs and simplified logistics.
- Among the various approaches to in vivo CAR engineering, LNP–mRNA-based CARs have a strong chance of reaching the clinic first, leveraging the manufacturing and regulatory advancements established during the COVID-19 pandemic.
- Preclinical proof-of-concept studies in cancer and cardiac injury models have demonstrated functional equivalence between therapeutic cells that were engineered in vivo and those produced via conventional ex vivo methods.
- Before taking in vivo CAR engineering to the clinic, it is essential to conduct a comparative analysis across the various vector technologies to identify those that provide an optimal balance among efficacy, immunogenicity and safety.
- Patient selection for in vivo CAR engineering would be likely to prioritize individuals with relatively intact immune systems, as endogenous T cells must respond to the in vivo gene delivery, expand and persist for therapeutic efficacy. This could exclude heavily pretreated patients with profound lymphopenia or those with a highly immunosuppressive TME.
𝐁𝐫𝐞𝐚𝐤𝐭𝐡𝐫𝐨𝐮𝐠𝐡 𝐢𝐧 𝐆𝐞𝐧𝐞 𝐓𝐡𝐞𝐫𝐚𝐩𝐲: Life-Changing Miracle for Baby with Fatal Disease 👇
Eisa Hussain, a four-year-old boy born with the severe form of leukocyte adhesion deficiency 1 (LAD-1), was given a "death sentence" without treatment.
This ultra rare disease cripples the immune system, often leading to death before age two.
👉 This innovative gene therapy, developed by Rocket Pharmaceuticals, used Eisa’s own stem cells at GOSH to replace the faulty gene responsible for the condition, restoring his immune system.
Now, several months after receiving the treatment, Eisa is thriving, playing football, attending school, and living a normal life something his family once thought impossible.
This incredible breakthrough is a beacon of hope for other families facing rare, life-threatening conditions.
Amazing to see just how powerful gene therapy is in saving lives 👏
#genetherapy #raredisease #celltherapy #CGTweekly | 26 commentaires sur LinkedIn
🚀 The Ultimate Guide to ADC Drugs 🚀 Want to know everything about the 17 approved ADC drugs worldwide in 2025? We've got you covered! From advanced cancer therapies to the latest treatment breakthroughs, this is the most comprehensive summary yet. 🔍 Discover: ✅ All 17 FDA-approved ADC drugs ✅ Key details on each drug's target and mechanism ✅ Global approval updates Don't miss out on the full breakdown! Click below to read the full article. ⬇️ https://lnkd.in/gAjYyszC #ADC #Pharma #DrugDevelopment #CancerTreatment #Biotech #Pharmaceuticals
Malaria vaccine research has progressed significantly, with RTS,S/AS01 and R21/Matrix-M receiving WHO endorsement in 2021 / 2023. These vaccines show promise, but challenges like vaccine adherence, strain variation, and resistance persist, highlighting the need for more effective, broad-reaching interventions.
Chimeric antigen receptor (CAR)-based therapies developed for the treatment of haematological malignancies have recently been repurposed to treat refractory systemic autoimmune diseases.
📖 In a NEW Review Marc Scherlinger and colleagues critically discuss the current data available on the use of CAR-based therapy in systemic autoimmune diseases, the current challenges, and the potential next steps toward their implementation into clinical practice. Beyond the targeting of B cells via CD19, the advantages and potential pitfalls of targeting plasma cells (B-cell Maturation Antigen or CD138) and other non-immune targets, such as fibroblast activated protein, and of aiming to restore immune homeostasis using CAR T regulatory cells, are also discussed.
Gavi and its partners have identified 11 needle-free vaccine patches that should be prioritised to boost immunisation coverage in low- and middle-income countries.
Manufacturing CAR NK cells at sufficient scale and quality for clinical use is no easy feat. Robust GMP-compliant protocols are essential, but strategies vary depending on the starting material and proprietary technologies.
Here’s a look at how different companies are tackling this challenge: 🩸 𝐏𝐁-𝐍𝐊 (𝐏𝐞𝐫𝐢𝐩𝐡𝐞𝐫𝐚𝐥 𝐁𝐥𝐨𝐨𝐝-𝐃𝐞𝐫𝐢𝐯𝐞𝐝 𝐍𝐊 𝐂𝐞𝐥𝐥𝐬) Companies like Nkarta, Inc. use healthy donor NK cells, activated with feeder cells and genetically modified using γ-retrovirus to introduce a CAR and IL-15. Cells are expanded and cryopreserved for off-the-shelf use. 🧬 𝐂𝐁-𝐍𝐊 (𝐂𝐨𝐫𝐝 𝐁𝐥𝐨𝐨𝐝-𝐃𝐞𝐫𝐢𝐯𝐞𝐝 𝐍𝐊 𝐂𝐞𝐥𝐥𝐬) Artiva Biotherapeutics and Takeda leverage donor CB units, selecting for high-affinity CD16 variants or KIR ligand mismatches to enhance anti-tumor activity. Genetic engineering (via lentivirus/retrovirus) introduces CAR and IL-15, followed by expansion and storage. 🦠 𝐢𝐏𝐒𝐂-𝐍𝐊 (𝐈𝐧𝐝𝐮𝐜𝐞𝐝 𝐏𝐥𝐮𝐫𝐢𝐩𝐨𝐭𝐞𝐧𝐭 𝐒𝐭𝐞𝐦 𝐂𝐞𝐥𝐥-𝐃𝐞𝐫𝐢𝐯𝐞𝐝 𝐍𝐊 𝐂𝐞𝐥𝐥𝐬) Fate Therapeutics Inc. uses a clonal iPSC master bank to generate NK cells, incorporating genetic modifications such as IL-15RF expression and CD38 knockout, enabling high-scale production. ⚡ 𝐍𝐊-𝟗𝟐 (𝐈𝐦𝐦𝐨𝐫𝐭𝐚𝐥𝐢𝐳𝐞𝐝 𝐍𝐊 𝐂𝐞𝐥𝐥 𝐋𝐢𝐧𝐞) Trials like NCT03383978 explore NK-92-based CAR NK cells, expanded under GMP conditions. Due to their tumorigenic nature, γ-irradiation is applied before infusion to prevent proliferation while maintaining potency.
Each approach presents unique advantages and challenges, shaping the future of off-the-shelf cell therapy. As technology advances, optimizing manufacturing efficiency and scalability will be key to ensuring broader patient access.
💬 What do you think is the most promising approach for CAR NK therapies ? Let’s discuss !
Vaccines are one of the most effective #PublicHealth tools in our toolbox. Combination vaccines, where one vaccine covers multiple diseases or strains, could…
Un médicament administré par injection une fois par an a la possibilité de prévenir l'infection par le VIH. Ceci pourrait changer complétement la donne en…
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