Immunology and Biotherapies
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#highlyviewed #covid19 #vaccines #sarscov2 | Pathogens MDPI

#highlyviewed #covid19 #vaccines #sarscov2 | Pathogens MDPI | Immunology and Biotherapies | Scoop.it
#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.


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Immunology and Biotherapies
Page Ressources et Actualités du DIU immunologie et biothérapies
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Scooped by Gilbert C FAURE
December 16, 2013 2:45 AM
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Resources for DIU Immunologie et Biothérapies

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:

We use Scoop.it as preferred curation tool to collect, select, comment informations flowing on the web in this rapidly evolving theme to keep teachers abreast of scientific knowledge and help students surf the wave...                                                            Feel free to be a follower!

 

If you are interested

in Immunology also use http://www.scoop.it/t/immunology

in Mucosal Immunity http://www.scoop.it/t/mucosal-immunity

in Flow Cytometry and Cytomics http://www.scoop.it/t/from-flow-cytometry-to-cytomics

in Allergy an Clinical Immunology http://www.scoop.it/t/allergy-and-clinical-immunology

in Autoimmunity http://www.scoop.it/t/autoimmunity

 

For further information on Immune monitoring of Immune therapies, 

http://www.scoop.it/t/immune-monitoring-1     by MdC

 

Looking for cancer applications inside this topic, use

http://www.scoop.it/t/immunology-and-biotherapies?q=cancer

 

Looking for cytokines and chemokines, use

http://www.scoop.it/t/cytokines-et-chimiokines

 

Thanks to K Maggon for joining us. @Krishan Maggon

 

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May 7, 11:19 AM
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#genetherapy #raredisease #celltherapy #cgtweekly | Spencer Knight | 26 commentaires

#genetherapy #raredisease #celltherapy #cgtweekly | Spencer Knight | 26 commentaires | Immunology and Biotherapies | Scoop.it
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
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April 22, 5:33 AM
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17 Approved ADCs Worldwide: The Ultimate Guide (Updated 2025) | Hunan Huateng Pharmaceutical Co., Ltd

17 Approved ADCs Worldwide: The Ultimate Guide (Updated 2025) | Hunan Huateng Pharmaceutical Co., Ltd | Immunology and Biotherapies | Scoop.it
🚀 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
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April 19, 2:29 AM
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Recent perspectives in clinical development of malaria vaccines | Nature Communications

Recent perspectives in clinical development of malaria vaccines | Nature Communications | Immunology and Biotherapies | Scoop.it
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.
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April 16, 7:32 AM
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#mrnadelivery #lipidnanoparticles #rnaformulation #nonviralvectors… | TechnoPharmaSphere

#mrnadelivery #lipidnanoparticles #rnaformulation #nonviralvectors… | TechnoPharmaSphere | Immunology and Biotherapies | Scoop.it
🚫 𝗡𝗼𝘁 𝗮𝗹𝗹 𝗺𝗥𝗡𝗔 𝗱𝗲𝗹𝗶𝘃𝗲𝗿𝘆 𝘀𝘆𝘀𝘁𝗲𝗺𝘀 𝗮𝗿𝗲 𝗯𝘂𝗶𝗹𝘁 𝘁𝗵𝗲 𝘀𝗮𝗺𝗲.

Some? Bare-bones.
Others? Engineered with surgical precision.

🧪 But every single one reveals something deeper—
---> Formulation strategy.
---> Biocompatibility.
---> How far we’ve come in drug delivery science.

👇 Here's a visual buffet of mRNA vaccine delivery platforms—each with its own size, mechanism, and logic:

📍 Naked mRNA – No carrier. Vulnerable. Fast degradation.
📍 Electroporation – A jolt to get inside cells. Effective, but tech-heavy.
📍 Protamine-complexed – Cationic peptide hugs mRNA. More stable, better uptake.
📍 Cationic nanoemulsion – Think oil-in-water with a positive twist.
📍 Dendrimer + PEG-lipid – Custom-designed for precision and low immunogenicity.
📍 Protamine in PEG-lipid NP – Double protection. Peptide inside, stealth outside.
📍 PEI-based – Potent. But needs careful formulation to avoid toxicity.
📍 PEI + lipids – A more balanced version for smoother biocompatibility.
📍 Polysaccharide-based – Like chitosan. Gentle and stable.
📍 Cationic lipid nanoparticles – Classic workhorses: DOTAP, DOPE, and friends.
📍 Cationic lipids + cholesterol ± PEG-lipid – Combo packs for optimal stability and immune modulation.

✨ And then there’s ex vivo dendritic cell loading:
💸 Pricey.
🕒 Time-consuming.
🎯 But unbeatable when precision targeting really matters.

💡 Bottom line:
In mRNA therapeutics, delivery isn’t just how you get there—it’s the whole mission.

It’s the difference between "potential" and "performance."

💬 What delivery tech are you watching (or working on) in this space?

👇 Let’s break down what works, what’s evolving, and what’s next.

#mRNADelivery #LipidNanoparticles #RNAFormulation #NonViralVectors #mRNATherapeutics #FormulationStrategy #TechnoPharmaSphere
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April 10, 9:54 AM
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Chimeric antigen receptor (CAR)-based therapies developed for the… | The Lancet Rheumatology

Chimeric antigen receptor (CAR)-based therapies developed for the… | The Lancet Rheumatology | Immunology and Biotherapies | Scoop.it
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.

Read the full Review here 👉 https://lnkd.in/eB7cvhGG

Alt text: Current and future strategies for CAR use in humans
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April 4, 11:51 AM
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11 needle-free vaccines that could transform global immunisation

11 needle-free vaccines that could transform global immunisation | Immunology and Biotherapies | Scoop.it
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.
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April 2, 12:22 PM
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The clinical landscape of CAR NK cells | Camille Bachelet

The clinical landscape of CAR NK cells | Camille Bachelet | Immunology and Biotherapies | Scoop.it
🏭 𝐌𝐚𝐧𝐮𝐟𝐚𝐜𝐭𝐮𝐫𝐢𝐧𝐠 𝐒𝐭𝐫𝐚𝐭𝐞𝐠𝐢𝐞𝐬 𝐟𝐨𝐫 𝐂𝐀𝐑 𝐍𝐊 𝐂𝐞𝐥𝐥 𝐓𝐡𝐞𝐫𝐚𝐩𝐢𝐞𝐬: 𝐂𝐡𝐚𝐥𝐥𝐞𝐧𝐠𝐞𝐬 & 𝐈𝐧𝐧𝐨𝐯𝐚𝐭𝐢𝐨𝐧𝐬

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 !

#CellTherapy #CellandGeneTherapy #CARNK #GMP #Manufacturing #Immunotherapy #Oncology
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March 28, 4:50 AM
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#tsemag #recherche #économie #orientation #innovation | Toulouse School of Economics

#tsemag #recherche #économie #orientation #innovation | Toulouse School of Economics | Immunology and Biotherapies | Scoop.it
📚🔬Innovation médicale et prix des médicaments : un équilibre économique à trouver

Nouveaux traitements, thérapies géniques, accès aux soins… Derrière chaque…
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March 27, 5:00 AM
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How combining vaccines saves money and lives | PATH

How combining vaccines saves money and lives | PATH | Immunology and Biotherapies | Scoop.it
Vaccines are one of the most effective #PublicHealth tools in our toolbox. Combination vaccines, where one vaccine covers multiple diseases or strains, could…
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March 14, 4:35 AM
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Nicolas Dauby MD, PhD on LinkedIn: Un médicament administré par injection une fois par an a la possibilité de…

Nicolas Dauby MD, PhD on LinkedIn: Un médicament administré par injection une fois par an a la possibilité de… | Immunology and Biotherapies | Scoop.it
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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March 9, 5:36 AM
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CAR-T vs CAR-NK therapies: How do they compare? Let's break it down: 1… | Benjamin McLeod | 80 comments

CAR-T vs CAR-NK therapies: How do they compare? Let's break it down: 1… | Benjamin McLeod | 80 comments | Immunology and Biotherapies | Scoop.it
CAR-T vs CAR-NK therapies:
How do they compare?
Let's break it down:

1. Relative Abundance in the Body
- CAR-T: T cells = ~30-60% of lymphocytes (easier… | 80 comments on LinkedIn
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Jean Daniel Lelièvre on LinkedIn: ISV Mini-Symposium on Pneumococcal Vaccines

Jean Daniel Lelièvre on LinkedIn: ISV Mini-Symposium on Pneumococcal Vaccines | Immunology and Biotherapies | Scoop.it
Interesting mini symposium
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Rescooped by Gilbert C FAURE from Hésitations Vaccinales: Observatoire HESIVAXs
May 8, 5:25 AM
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Nasal vaccines for respiratory infections

Nasal vaccines for respiratory infections | Immunology and Biotherapies | Scoop.it
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.
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April 30, 6:47 AM
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Frontiers | European survey on CAR T-Cell analytical methods from… | Hélène NEGRE

Frontiers | European survey on CAR T-Cell analytical methods from… | Hélène NEGRE | Immunology and Biotherapies | Scoop.it
#T2Evolve survey results on analytical methods for CAR T cells. A nice overview of the European landscape !
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April 19, 4:24 AM
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Intranasal spike and nucleoprotein fusion protein-based vaccine provides cross-protection and reduced transmission against SARS-CoV-2 variants | npj Vaccines

Intranasal spike and nucleoprotein fusion protein-based vaccine provides cross-protection and reduced transmission against SARS-CoV-2 variants | npj Vaccines | Immunology and Biotherapies | Scoop.it
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.
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April 17, 7:03 AM
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JCI - Developing cell-based therapies for pancreatic ductal adenocarcinoma

JCI - Developing cell-based therapies for pancreatic ductal adenocarcinoma | Immunology and Biotherapies | Scoop.it
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.
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April 13, 7:52 AM
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#highlyviewed #covid19 #vaccines #sarscov2 | Pathogens MDPI

#highlyviewed #covid19 #vaccines #sarscov2 | Pathogens MDPI | Immunology and Biotherapies | Scoop.it
#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.


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April 7, 3:40 AM
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Latest Vaccine Advances: RSV, Mpox, Cancer, COVID & Allergy

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.
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April 3, 6:02 AM
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#immunotherapy #autoimmunediseases #cancer #transplantation… | John Gordon

#immunotherapy #autoimmunediseases #cancer #transplantation… | John Gordon | Immunology and Biotherapies | Scoop.it
#Immunotherapy | #AutoimmuneDiseases | #Cancer | #Transplantation | The Role of #RegulatoryTcells ↔ #Endothelial Cells Crosstalk | Breaking Perspective at…
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March 27, 5:10 AM
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#mrna #covid19 #vaccines #geneexpression #dna #immunesystem #pathogens… | Melvin Sanicas

#mrna #covid19 #vaccines #geneexpression #dna #immunesystem #pathogens… | Melvin Sanicas | Immunology and Biotherapies | Scoop.it
🧬 𝗡𝗲𝘄 𝗦𝘁𝘂𝗱𝘆 𝗥𝗲𝘃𝗲𝗮𝗹𝘀 𝗛𝗼𝘄 𝗺𝗥𝗡𝗔 𝗖𝗢𝗩𝗜𝗗-𝟭𝟵 𝗩𝗮𝗰𝗰𝗶𝗻𝗲𝘀 𝗧𝗿𝗮𝗶𝗻 𝘁𝗵𝗲 𝗜𝗺𝗺𝘂𝗻𝗲 𝗦𝘆𝘀𝘁𝗲𝗺’𝘀 '𝗟𝗼𝗻𝗴-𝗧𝗲𝗿𝗺…
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The puzzle of biologics manufacturing platform patents - Nature… | Osmat Azzam Jefferson

The puzzle of biologics manufacturing platform patents - Nature… | Osmat Azzam Jefferson | Immunology and Biotherapies | Scoop.it
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…
Gilbert C FAURE's insight:

patents

https://www.scoop.it/topic/immunology-and-biotherapies?q=patents

 

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March 10, 5:06 AM
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Spencer Knight on LinkedIn: #oncology #immunology #celltherapy #cgtweekly | 24 comments

Spencer Knight on LinkedIn: #oncology #immunology #celltherapy #cgtweekly | 24 comments | Immunology and Biotherapies | Scoop.it
𝐂𝐀𝐑 𝐓 𝐓𝐡𝐞𝐫𝐚𝐩𝐲 𝐢𝐧 𝐍𝐨𝐧-𝐎𝐧𝐜𝐨𝐥𝐨𝐠𝐲 👇

CAR T cell therapy has transformed cancer treatment, but its potential extends far beyond oncology.… | 24 comments on LinkedIn
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February 20, 6:40 AM
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RNA neoantigen vaccines prime long-lived CD8+ T cells in pancreatic cancer

RNA neoantigen vaccines prime long-lived CD8+ T cells in pancreatic cancer | Immunology and Biotherapies | Scoop.it
A fundamental challenge for cancer vaccines is to generate long-lived functional T cells that are specific for tumour antigens. Here we find that mRNA–lipoplex vaccines against somatic mutation-derived neoantigens may solve this challenge in pancreatic ductal adenocarcinoma (PDAC), a lethal cancer with few mutations. At an extended 3.2-year median follow-up from a phase 1 trial of surgery, atezolizumab (PD-L1 inhibitory antibody), autogene cevumeran1 (individualized neoantigen vaccine with backbone-optimized uridine mRNA–lipoplex nanoparticles) and modified (m) FOLFIRINOX (chemotherapy) in patients with PDAC, we find that responders with vaccine-induced T cells (n = 8) have prolonged recurrence-free survival (RFS; median not reached) compared with non-responders without vaccine-induced T cells (n = 8; median RFS 13.4 months; P  =  0.007). In responders, autogene cevumeran induces CD8+ T cell clones with an average estimated lifespan of 7.7 years (range 1.5 to roughly 100 years), with approximately 20% of clones having latent multi-decade lifespans that may outlive hosts. Eighty-six percent of clones per patient persist at substantial frequencies approximately 3 years post-vaccination, including clones with high avidity to PDAC neoepitopes. Using PhenoTrack, a novel computational strategy to trace single T cell phenotypes, we uncover that vaccine-induced clones are undetectable in pre-vaccination tissues, and assume a cytotoxic, tissue-resident memory-like T cell state up to three years post-vaccination with preserved neoantigen-specific effector function. Two responders recurred and evidenced fewer vaccine-induced T cells. Furthermore, recurrent PDACs were pruned of vaccine-targeted cancer clones. Thus, in PDAC, autogene cevumeran induces de novo CD8+ T cells with multiyear longevity, substantial magnitude and durable effector functions that may delay PDAC recurrence. Adjuvant mRNA–lipoplex neoantigen vaccines may thus solve a pivotal obstacle for cancer vaccination. In a phase 1 trial, patients with pancreatic ductal adenocarcinoma who were treated with surgery and bespoke neoantigen mRNA vaccines combined with anti-PD-L1 and chemotherapy exhibited marked long-lived persistence of neoantigen-specific CD8+ T cell clones, which correlated with prolonged recurrence-free survival at a 3.2-year follow-up.
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February 4, 1:28 PM
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Novel strategies to manage CAR-T cell toxicity | Nature Reviews Drug Discovery

Novel strategies to manage CAR-T cell toxicity | Nature Reviews Drug Discovery | Immunology and Biotherapies | Scoop.it
The immune-related adverse events associated with chimeric antigen receptor (CAR)-T cell therapy result in substantial morbidity as well as considerable cost to the health-care system, and can limit the use of these treatments. Current therapeutic strategies to manage immune-related adverse events include interleukin-6 receptor (IL-6R) blockade and corticosteroids. However, because these interventions do not always address the side effects, nor prevent progression to higher grades of adverse events, new approaches are needed. A deeper understanding of the cell types involved, and their associated signalling pathways, cellular metabolism and differentiation states, should provide the basis for alternative strategies. To preserve treatment efficacy, cytokine-mediated toxicity needs to be uncoupled from CAR-T cell function, expansion, long-term persistence and memory formation. This may be achieved by targeting CAR or independent cytokine signalling axes transiently, and through novel T cell engineering strategies, such as low-affinity CAR-T cells, reversible on–off switches and versatile adaptor systems. We summarize the current management of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, and review T cell- and myeloid cell-intrinsic druggable targets and cellular engineering strategies to develop safer CAR-T cells. Treatment with chimeric antigen receptor (CAR)-T cell therapies is associated with important immune-related adverse events. In this Review, the authors discuss the standard-of-care management for cytokine release and immune effector cell-associated neurotoxicity syndromes, and the potential of other T cell druggable targets as well as cellular engineering strategies to develop safer CAR-T cells.
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