Some? Bare-bones. Others? Engineered with surgical precision.
๐งช But every single one reveals something deeperโ ---> Formulation strategy. ---> Biocompatibility. ---> How far weโve come in drug delivery science.
๐ Here's a visual buffet of mRNA vaccine delivery platformsโeach with its own size, mechanism, and logic:
๐ Naked mRNA โ No carrier. Vulnerable. Fast degradation. ๐ Electroporation โ A jolt to get inside cells. Effective, but tech-heavy. ๐ Protamine-complexed โ Cationic peptide hugs mRNA. More stable, better uptake. ๐ Cationic nanoemulsion โ Think oil-in-water with a positive twist. ๐ Dendrimer + PEG-lipid โ Custom-designed for precision and low immunogenicity. ๐ Protamine in PEG-lipid NP โ Double protection. Peptide inside, stealth outside. ๐ PEI-based โ Potent. But needs careful formulation to avoid toxicity. ๐ PEI + lipids โ A more balanced version for smoother biocompatibility. ๐ Polysaccharide-based โ Like chitosan. Gentle and stable. ๐ Cationic lipid nanoparticles โ Classic workhorses: DOTAP, DOPE, and friends. ๐ Cationic lipids + cholesterol ยฑ PEG-lipid โ Combo packs for optimal stability and immune modulation.
โจ And then thereโs ex vivo dendritic cell loading: ๐ธ Pricey. ๐ Time-consuming. ๐ฏ But unbeatable when precision targeting really matters.
๐ก Bottom line: In mRNA therapeutics, delivery isnโt just how you get thereโitโs the whole mission.
Itโs the difference between "potential" and "performance."
๐ฌ What delivery tech are you watching (or working on) in this space?
๐ Letโs break down what works, whatโs evolving, and whatโs next.
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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IL-7โexpanded CD8+ T cells demonstrate increased accumulation within orthotopic glioblastoma models despite endogenous T cell sequestration in bone marrow. Though peripherally administered, activated autologous T cells have been shown to cross the BBB under physiologic conditions (28), their...
Exciting see the next-gen CARs tackle areas beyond oncology. Dual-targeting CARs (e.g., CD19-BCMA for lupus) are proving especially effective in tackling treatment-resistant diseases.
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, LNPโmRNA-based CARs have a strong chance of reaching the clinic first, leveraging the manufacturing and regulatory advancements established during the COVID-19 pandemic.
-ย 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 exย 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 beย likely toย 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 aย highly immunosuppressive TME.
๐๐ซ๐๐๐ค๐ญ๐ก๐ซ๐จ๐ฎ๐ ๐ก ๐ข๐ง ๐๐๐ง๐ ๐๐ก๐๐ซ๐๐ฉ๐ฒ: Life-Changing Miracle for Baby with Fatal Disease ๐
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.
๐ This innovative gene therapy, developed by Rocket Pharmaceuticals, used Eisaโs 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 ๐
#genetherapy #raredisease #celltherapy #CGTweekly | 26 commentaires sur LinkedIn
๐ The Ultimate Guide to ADC Drugs ๐ 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. ๐ Discover: โ All 17 FDA-approved ADC drugs โ Key details on each drug's target and mechanism โ Global approval updates Don't miss out on the full breakdown! Click below to read the full article. โฌ๏ธ 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.
Some? Bare-bones. Others? Engineered with surgical precision.
๐งช But every single one reveals something deeperโ ---> Formulation strategy. ---> Biocompatibility. ---> How far weโve come in drug delivery science.
๐ Here's a visual buffet of mRNA vaccine delivery platformsโeach with its own size, mechanism, and logic:
๐ Naked mRNA โ No carrier. Vulnerable. Fast degradation. ๐ Electroporation โ A jolt to get inside cells. Effective, but tech-heavy. ๐ Protamine-complexed โ Cationic peptide hugs mRNA. More stable, better uptake. ๐ Cationic nanoemulsion โ Think oil-in-water with a positive twist. ๐ Dendrimer + PEG-lipid โ Custom-designed for precision and low immunogenicity. ๐ Protamine in PEG-lipid NP โ Double protection. Peptide inside, stealth outside. ๐ PEI-based โ Potent. But needs careful formulation to avoid toxicity. ๐ PEI + lipids โ A more balanced version for smoother biocompatibility. ๐ Polysaccharide-based โ Like chitosan. Gentle and stable. ๐ Cationic lipid nanoparticles โ Classic workhorses: DOTAP, DOPE, and friends. ๐ Cationic lipids + cholesterol ยฑ PEG-lipid โ Combo packs for optimal stability and immune modulation.
โจ And then thereโs ex vivo dendritic cell loading: ๐ธ Pricey. ๐ Time-consuming. ๐ฏ But unbeatable when precision targeting really matters.
๐ก Bottom line: In mRNA therapeutics, delivery isnโt just how you get thereโitโs the whole mission.
Itโs the difference between "potential" and "performance."
๐ฌ What delivery tech are you watching (or working on) in this space?
๐ Letโs break down what works, whatโs evolving, and whatโs next.
Chimeric antigen receptor (CAR)-based therapies developed for the treatment of haematological malignancies have recently been repurposed to treat refractory systemic autoimmune diseases.
๐ 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.
Effects of different B-cell-depleting strategies on the lymphatic tissue
- Advanced protein-based B cell depleters, such as glycoengineered CD20 monoclonal antibody obinutuzumab (OBI) and CD19/CD3 T cell engager blinatumomab (BLI), are promising new therapeutic instruments for treatment of autoimmune disease (AIDs).
- It has been speculated that such B cell-depleting modalities achieve better clearance of tissue B cells in patients.
- By performing sequential lymph node biopsies, this study shows that advanced protein-based B cell depleters, like OBI and BLI, reduce but do not consistently deplete B cells in the lymph nodes.
- These results stand in contrast to the consistent full depletion of B cells associated with the disruption of follicular lymph node architecture after CD19 chimeric antigen receptor T cell therapy.
- B cell depletion was associated with stable drug-free remission, whereas a reduction in B cell numbers without depletion required retreatment with immunomodulatory drugs.
- ย Introducing lymph node biopsy as a clinical tool to assess B cell depletion could enhance treatment monitoring and play a pivotal role in tailoring therapeutic strategies. ย Larger-scale studies are needed to confirm whether B cell depletion in secondary lymphoid organs directly correlates with clinical outcomes in patients with AID.
The FLUniversal consortium, supported by the EUโs Horizon Europe programme, is pioneering the development of an intranasal universal influenza vaccine. Our goal is to create a vaccine that offers broad protection against all flu strains, reducing the need for annual updates. ย Key highlights of our approach include: - Innovative Vaccine Design: Utilizing a live, replication-deficient influenza strain lacking the NS1 protein to stimulate a robust and lasting immune response. - Intranasal Delivery: Administering the vaccine through the nose to induce strong local immunity, potentially preventing infection at its entry point. - Comprehensive Testing: Employing controlled human infection models (CHIMs) to assess vaccine efficacy and identify immune correlates of protection. - Preclinical Validation: Animal studies have demonstrated promising safety and immunogenicity results, laying a solid foundation for future clinical development. ย This collaborative effort brings together leading experts from academia and industry, aiming to revolutionize influenza prevention. ย Read the full article here: https://lnkd.in/dpYwW-PV
Thrilled to have attended last weekโs virtual "๐๐ฃ ๐๐๐ซ๐ค ๐๐ฃ๐๐๐ฃ๐๐๐ง๐๐ฃ๐ ๐ค๐ ๐๐ข๐ข๐ช๐ฃ๐ ๐พ๐๐ก๐ก๐จ (๐๐๐๐๐พ)" workshop hosted by the ๐ก๐๐! ๐
๐๐ฏ ๐ท๐ช๐ท๐ฐ cell engineering is redefining the possibilities of immunotherapyโoffering the potential for ๐ณ๐ฎ๐๐๐ฒ๐ฟ, ๐บ๐ผ๐ฟ๐ฒ ๐ฎ๐ฐ๐ฐ๐ฒ๐๐๐ถ๐ฏ๐น๐ฒ, ๐ฎ๐ป๐ฑ ๐น๐ฒ๐๐ ๐ฟ๐ฒ๐๐ผ๐๐ฟ๐ฐ๐ฒ-๐ถ๐ป๐๐ฒ๐ป๐๐ถ๐๐ฒ treatments compared to traditional ๐ฆ๐น ๐ท๐ช๐ท๐ฐ approaches.
๐ฆ๐ผ๐บ๐ฒ ๐ธ๐ฒ๐ ๐ฎ๐ฑ๐๐ฎ๐ป๐๐ฎ๐ด๐ฒ๐ ๐ถ๐ป๐ฐ๐น๐๐ฑ๐ฒ: โ No need for GMP manufacturing facilities โ Shorter and more scalable workflows โ Potential for outpatient or point-of-care delivery
โ ๏ธ ๐๐๐ ๐ฐ๐ต๐ฎ๐น๐น๐ฒ๐ป๐ด๐ฒ๐ ๐ฟ๐ฒ๐บ๐ฎ๐ถ๐ป: - Reduced control over the engineering process - Difficulties in targeting specific immune subsets - Efficacy and safety still under active investigation
- Carl June (University of Pennsylvania) laid the groundwork with a visionary keynote on ๐ฆ๐น ๐ท๐ช๐ท๐ฐ and ๐ช๐ฏ ๐ท๐ช๐ท๐ฐ CAR-T.
- Matthias Stephan (WHI CCC Fred Hutchinson Cancer Research Center) showcased the power of local reprogramming via ๐ช๐ฏ ๐ท๐ช๐ท๐ฐ 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 ๐ช๐ฏ ๐ท๐ช๐ท๐ฐ reprogramming.
- Daniel G. (Myeloid Therapeutics) shared early clinical data on ๐ช๐ฏ ๐ท๐ช๐ท๐ฐ mRNA CAR myeloid engineering.
- Adrian Bot, M.D., Ph.D. (Capstan Therapeutics) presented Capstanโs LNP platform tackling both oncology and autoimmunity.
๐ 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 Jennerโs 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 ๐ข An Update on Anti- #COVID19 #Vaccines and the Challenges to Protect Against New #SARSCoV2 Variants ๐จโ๐ by Fรกbio Mambelli et al. ๐ 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, Modernaโs 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.
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