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Discovered more than 30 years ago, CD40L antagonists are proving to be powerful autoimmune drugs.

Learn more in a 2024 #SciencePerspective: https://scim.ag/3KfDHGc #ScienceMagArchives

The age of immunotherapy for type 1 diabetes is upon us! Thrilled by the opportunity to contribute to this review led by Remi Creusot at Columbia University!#immunologymatters #endt1d https://lnkd.in/eQ_E2j5d

Important issue!

Vaccines are a polarizing topic right now—easier to say it than ignore it.

But what isn’t polarizing is this: there are people and service members in remote, underserved, and conflict-affected parts of the world still vulnerable to some of the deadliest diseases on earth because of a lack of infrastructure. Diseases like Ebola and Marburg. And protection from them still requires deep freezers and trained clinicians to prepare and administer today’s tools.

Today, we announced new stability data on our intranasal vaccine candidate—a platform built on a well-established vector designed not just with the intention to protect, but to reach.

Grateful to everyone involved so far. Still more work to do, but this moonshot may just have legs. #AMR #Access

🐘 The first #mRNA vaccine for elephants!

Elephant endotheliotropic herpesvirus (EEHV) is the leading killer of baby Asian elephants. Professor Paul Ling at Baylor College of Medicine teamed up with Houston Zoo to develop a preventative vaccine using #mRNA technology. With support from Colossal Biosciences (the de-extinction/wooly mice company) they have evaluated the vaccine preclinically and have dosed their first elephant.

While #mRNA medicines for humans may get most of the headlines, development of applications for animal health are also accelerating.

Article: https://lnkd.in/gc_HPPB5

🚨#Immunogenicity can undermine any biologic, driven by anti-drug-antibodies (#ADA), from pre-clinical to post launch. This topic is so challenging due to the combination, intricacies and complexity of the molecules, human immunology, patient treatment journeys, assay standards and the vagaries of publishing. There is a ground truth but “for now we see through a glass, darkly”. Allowing for all that complexity, and briefly putting it to one side, are there any rules of thumbs we can see?

🫣What data shall we look at?

I decided to focus on the worst-case scenario and use the maximal ADA rates (the % of HV or patients across phase 1-4 reporting ADA post treatment) for #antibodies. With the help of a Deep Research tool I read the refs and extracted the published maximal ADA rates for these assets across all indications. So that’s:
• 54 #bisAb: 19 approved & 2 reg review, 13 phase 1-3, 20 terminated phase 1-3
• 129 #mAb: 75 approved | 16 phase 1-3 | 38 terminated phase 1-3

🎬 Findings:

1️⃣ mAb and bisAb clinical assets have a #similar spread of ADA profiles. The same observation was published this year in the IQ Survey Part 2 on immunogenicity for 46 mAb and 9 bisAb assets.
2️⃣ Mixtures of mAbs, co-formulated or co-administered, do not reduce immunogenicity risk.
3️⃣ Some targets do report higher ADA rates for almost all mAb and bisAb prosecuted in the clinic. This may primarily be MoA related but may also be due to the number of shots on goal the industry has tried.

🧐So what?

➡️ Each molecule is unique in its ADA risk profile. As we engineer our candidate drugs integrating an Immunogenicity Risk Assessment (#IRA) as part of our candidate target profile informs the risk and helps us select the candidate for IND.
🔂 The #translational #gap between the range of brilliant in vitro assays and patient response is still there.
↔️ Thank you to all the #patients, institutes and companies who put their data into the #public domain. As much as it’s in your remit please keep publishing the clinical ADA data. It’s part of enabling bedside to bench translation so we can do better next time💙

👍Over to #you🤔

❓What’s your view on de-risking preclinically and in vitro #assays?
🙋Who is curating this clinical data in a more robust way?

💬 it’s always good to chat the science through as “the truth is so obscure in these times… unless we love the truth, we can not know it” Blaise Pascal (1623-1662)

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.

-  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.  Larger-scale studies are needed to confirm whether B cell depletion in secondary lymphoid organs directly correlates with clinical outcomes in patients with AID.

https://lnkd.in/eDdFr-_7

#autoimmunity #celltherapy #immunology #rheumatology

The FLUniversal consortium, supported by the EU’s 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.
 
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.
 
This collaborative effort brings together leading experts from academia and industry, aiming to revolutionize influenza prevention.
 
Read the full article here: https://lnkd.in/dpYwW-PV

Professor Richard Scolyer, co-director of the Melanoma Institute Australia, has made medical history by becoming the first person to treat his own incurable brain cancer — glioblastoma — with immunotherapy. One year after his diagnosis, he now shows no detectable signs of the disease, a breakthrough that stunned the global medical community.


Scolyer used an experimental treatment adapted from his pioneering melanoma research, combining checkpoint inhibitor immunotherapy with surgery, chemotherapy, and radiation. By essentially reprogramming his immune system to attack the tumor, he achieved results never before seen in such aggressive cancers. While his case is unique, it opens a powerful new door for future brain cancer therapies, proving that innovation and courage can push the boundaries of science.


#CancerResearch #Immunotherapy #BrainCancer #MedicalBreakthrough #RichardScolyer | 136 comments on LinkedIn

🌐 Natural Killer Cells: The Next Frontier in Cancer Immunotherapy
For decades, cancer immunotherapy has focused on T cells, yet Natural Killer (NK) cells are emerging as equally powerful players with unique advantages.
🔬 What makes NK cells special?
They kill tumor cells without prior sensitization
They balance signals from activating (NKG2D, DNAM-1, NCRs) and inhibitory receptors (KIRs, NKG2A, TIGIT, PD-1)
They are less prone to causing cytokine release syndrome (CRS) or graft-versus-host disease (GVHD), making them safer platforms
⚠️ But tumors fight back:
Shedding of NKG2D ligands (MICA/B) via ADAM proteases creates soluble decoys that block NK activity
Immunosuppressive tumor microenvironment (Tregs, MDSCs, TAMs, TGF-β, IL-10, adenosine) dampens NK infiltration and cytotoxicity
Checkpoint pathways like TIGIT and PD-1 reduce NK function
💡 Therapeutic innovations on the horizon:
Cytokine-driven expansion (IL-15, IL-21) to boost NK persistence without fueling Tregs
CAR-NK cells – engineered for precision, combining innate and adaptive killing mechanisms, with improved safety profiles
Combination strategies with chemotherapy, radiotherapy, checkpoint blockade, and monoclonal antibodies to enhance ADCC and tumor clearance
🚀 The vision: Harnessing NK cells as an “off-the-shelf” immunotherapy — scalable, safer, and accessible. While persistence and tumor evasion remain challenges, the progress in CAR-NK engineering, checkpoint modulation, and biomarker-driven strategies could make NK-based therapies a cornerstone of next-generation oncology.
#CancerImmunotherapy #NKCells #CARNK #CellTherapy #GeneEditing #ImmunoOncology #OncologyInnovation #Biotechnology #MedicalResearch #CheckpointInhibitors #PrecisionOncology #FutureOfHealthcare #Immunotherapy #NextGenerationMedicine #MedicalInnovation

Interesting paper
From ClinicalTrial.gov, the main different antigens targeted by CART-cells (Liquid and solid tumors) and how many times they have been (or are currently being) evaluated in clinical trials.
Not yet for IL-1RAP!

Significant regulatory shift in UK
that may impact 𝗖𝗔𝗥-𝗧 delivery:
At-patient manufacturing!
 
With summer holidays and other industry happening, this news may have passed you by (it did me!):

As of 23rd July 2025, the MHRA (the UK regulator) legally allows flexible, innovative manufacturing approaches such as Point-of-Care and decentralised/distributed modular manufacturing for ATMPs including CAR-Ts.
 
𝗪𝗵𝗮𝘁’𝘀 𝘁𝗵𝗲 𝗯𝗮𝗰𝗸𝗴𝗿𝗼𝘂𝗻𝗱 𝗳𝗼𝗿 𝘁𝗵𝗶𝘀:

🔹 MHRA innovation office has been receiving enquiries around this kind of manufacturing since 2014 – but no regulatory framework was in place to allow for PoC or modular manufacturing.
🔹 As technology advances – particularly ATMPs – new manufacturing modalities are required that can take place in hospitals, clinics and even the patients own home!

💭 𝗜𝗺𝗮𝗴𝗶𝗻𝗲 𝘁𝗵𝗮𝘁, 𝗵𝗮𝘃𝗶𝗻𝗴 𝗮𝗻 𝗮𝘂𝘁𝗼𝗹𝗼𝗴𝗼𝘂𝘀 𝗖𝗔𝗥-𝗧 𝗺𝗮𝗻𝘂𝗳𝗮𝗰𝘁𝘂𝗿𝗲𝗱 𝗮𝗻𝗱 𝗱𝗲𝗹𝗶𝘃𝗲𝗿𝗲𝗱 𝘄𝗶𝘁𝗵𝗶𝗻 𝘆𝗼𝘂𝗿 𝗼𝘄𝗻 𝗵𝗼𝗺𝗲.


𝗛𝗼𝘄 𝘄𝗶𝗹𝗹 𝗶𝘁 𝘄𝗼𝗿𝗸?

🔹  The technical solutions are still in development. Notably, Spain has made some great progress on establishing localised CAR-T production centres in Barcelona and Navarra.
🔹 A centralised “Hub” control site will be responsible for the decentralised “Spoke” sites; being responsible for documentation, quality, release and inspections.
🔹 A Decentralised Manufacturing Master File (DM MF) is required to be managed by the control site with annual reporting to MHRA
🔹 GMP and Pharmacovigilance requirements are maintained and must be have appropriate management plans prior to approval
 
𝗜𝗻 𝘀𝘂𝗺𝗺𝗮𝗿𝘆:

This legislation marks a significant regulatory shift, accommodating disruptive innovation in medicine manufacture and delivery. MHRA has adopted a flexible, guidance-led approach supported by stakeholder feedback, with a strong emphasis on collaboration and quality assurance.

Links to the MHRA webinar and the guidance document in the comments 👇

𝗧𝗵𝗶𝘀 𝗵𝗮𝘀 𝗯𝗲𝗲𝗻 𝗵𝗮𝗶𝗹𝗲𝗱 𝗮𝘀 𝗮 𝗳𝗶𝗿𝘀𝘁 𝗮𝗺𝗼𝗻𝗴 𝗿𝗲𝗴𝘂𝗹𝗮𝘁𝗼𝗿𝘀 – but do you think this puts the UK in a strong position for systems developers? 
💬 As always, let me know your thoughts in the comments below. | 26 comments on LinkedIn

📣 We have today announced the launch of the world’s first library of immune-boosting adjuvants that can be ‘taken off the shelf’ and used to enhance new vaccines being developed against epidemic and pandemic threats.

The $2.5 million project—funded and led by CEPI—will act as a matchmaking service, helping vaccine developers select the best vaccine-adjuvant combinations to make their vaccines more potent and effective. The UK’s Medicines and Healthcare products Regulatory Agency will host the repository of 25 adjuvants shared by leading research institutes and medical companies around the world.
 
Vaccine-enhancing adjuvants have played a powerful role in transforming our response to deadly diseases over the past century. The ingredients are added to the majority of vaccines to enhance the immune response, creating stronger and longer lasting protection against infections than the vaccine alone.

In the case of an outbreak of a new Disease X, the adjuvant library could help quickly identify the top-performing vaccine-adjuvant pairings to contain the spread of the virus before it reaches pandemic proportions. 
 
🔗 Discover more in the link below.

Ever wondered about monoclonal antibody applications? The image contains every FDA-approved monoclonal antibody arranged by therapeutic areas.

Bi- and tri-specific antibodies are hot topics, but classical monoclonals (mAbs) are the workhorses of modern biotherapeutics.

In 1975, Georges Köhler and César Milstein, working in Cambridge, unlocked a new era of medicine with the development of the hybridoma technique.

That was the first method for mass-producing mAbs.

The first therapeutic mAb (Orthoclone OKT3) was approved in 1986, but there are now >100 FDA-approved mAbs.

➟ Oncology and haematology remain dominant applications of mAbs.

➟ Neurology and dermatology are growing fast with CGRP blockers and IL-23/IL-17 inhibitors.

➟ Interestingly, nearly 40 % of approvals are outside of cancer. I thought it would have been less.

Do you think bi-specifics will catch up?

---

* Data source: The Antibody Society.

** Some antibodies are approved for multiple therapeutic areas, and commercial rights may vary across jurisdictions or under specific licensing agreements.

#Immunotherapy | "Right Time, Right Place" | Lymph Node-targeted temporally programmed #STING nanoadjuvant delivery unlocks synergistic chemotherapy-induced anti-#Tumor #Immunity | Breaking at Science Magazine Advances |

Stimulator of interferon genes (STING) agonists have attracted notable attention for their potent immune activation capabilities. However, their clinical application is hindered by systemic toxicity and delivery inefficiencies.

Here*, researchers addressed these challenges by developing a lymph node–targeted STING agonist nanoadjuvant (Mn/MSA-2@Lipo) combined with a temporally optimized delivery strategy. Mn/MSA-2@Lipo uses manganese ions to amplify STING pathway activation while achieving efficient lymph node accumulation and antigen presentation.

They first induced immunogenic cell death (ICD) through chemotherapy to release tumor antigens, followed by the administration of the nanoadjuvant at an optimized time interval, the approach effectively synchronizes dendritic cell (DC) antigen uptake and maturation. This combination therapy notably enhanced antitumor immunity in melanoma and breast cancer models, achieving complete tumor regression and inducing long-lasting immune memory, all while demonstrating an excellent safety profile.

These findings highlight the critical importance of delivery timing optimization, offering a promising strategy for the clinical translation of STING agonists and the design of advanced immunotherapies.

*https://lnkd.in/epVJs-GE

Celentyx Ltd #immunooncology #drugdiscovery www.celentyx.com

Professor Nicholas Barnes PhD, FBPhS Omar Qureshi Catherine Brady

SUMMARY FIGURE | (A) Schematic of temporally programmed STING nanoadjuvant delivery unlocks synergistic chemotherapy-induced antitumor immunity | (B). Schematic representation of the temporally programmed delivery strategy. The top panel illustrates the optimal sequence of chemotherapy and nanoadjuvant delivery. Administering Mn/MSA-2@Lipo 48 hours after Doxil allows DCs to capture tumor antigens prior to maturation, enabling efficient cross-presentation to CD8+ T cells in the tdLNs. This strategy enhances CD8+ T cell activation, subsequent tumor cell destruction, and long-term immune memory. The bottom panel depicts premature adjuvant administration, leading to early DC maturation, reduced phagocytic capacity, and diminished antitumor immune responses |

IL-7–expanded 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...