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…
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.
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.
#Immunotherapy | #Cancer | In Case Anyone has Missed this PHENOMENAL Study / Resource posted last week : "A pan-Cancer #Atlas of #Tcell #Targets" | OPEN ACCESS…
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…
Organ and tissue damage, particularly of the musculoskeletal system, is commonly encountered in the clinic and can impact patient quality of life. Reconstructive operations can be necessary to restore form and function to damaged tissues; however, available off-the-shelf products fail to meet the needs of individual patients. Personalized regenerative treatments to restore damaged tissues could potentially bring benefits to both clinicians and patients. For example, resorbable implant scaffolds can be bioengineered and customized using technologies such as 3D printing to address the specific needs of patients while offering improved clinical outcomes along with reduced surgical time and complexity. For this purpose, appropriate medical-grade materials, advanced multiscale fabrication techniques and regulatory compliance are required. In this Review, we summarize the key considerations for developing personalized bioengineered implant scaffolds, emphasizing good manufacturing practice and clinical translatability. We discuss the status of clinical translation for personalized bioengineered implants and the lessons learned from existing phase I clinical trials using craniofacial reconstruction as a model system. Additionally, we provide a framework to inform wider clinical translation with recommendations on rational biomaterial choice and design, biofabrication strategies, biofunctionalization, standardized workflow, compliance with regulatory requirements, and evaluation of benefits. Finally, we discuss the remaining challenges and provide an outlook for the translation of personalized bioengineered implant scaffolds into routine clinical practice. Personalized bioengineered implant scaffolds offer customizable medical solutions for tissue and organ regeneration. This Review provides a framework for navigating the regulatory process and addressing challenges in technical development and biofabrication to ensure clinical translation of personalized devices.
Vaccines and treatments are up for approval in early to mid-2025, including a chikungunya vaccine, a meningococcal vaccine, a monoclonal antibody for RSV, and more.
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