Search Results (2,717)

Therapeutic cancer vaccines represent a rational immunotherapeutic strategy aimed at inducing tumor-specific adaptive immune responses in patients with established malignancies. In contrast to prophylactic vaccines, these approaches must function within immunosuppressive tumor microenvironments characterized by antigenic heterogeneity, immune dysfunction, and dynamic tumor evolution. Effective vaccine design requires the integration of three essential components: the selection of appropriate tumor-associated or tumor-specific antigens, efficient delivery platforms that enable antigen presentation, and adjuvant systems that promote robust T-cell priming and expansion. Initial clinical investigations in B-cell malignancies and multiple myeloma demonstrated that idiotype-based vaccines can elicit tumor-specific immune responses. However, durable clinical benefit has been inconsistent, reflecting limitations in antigen selection, suboptimal immunogenicity, and tumor-mediated immune evasion. Over the past decade, advances in tumor genomics, next-generation sequencing, and immune monitoring have enabled the development of next-generation vaccine platforms, including dendritic cell-based approaches, personalized neoantigen vaccines, and mRNA-based technologies. Emerging evidence suggests that vaccine efficacy is highly dependent on disease context. Biologically favorable settings such as minimal residual disease (MRD) and post-transplant immune reconstitution provide reduced tumor burden and improved immune competence, thereby enhancing the likelihood of effective immune priming. In parallel, combination strategies incorporating immune checkpoint inhibitors, immunomodulatory agents, and cellular therapies are increasingly being explored to overcome tumor-induced immunosuppression. This review synthesizes current knowledge of therapeutic cancer vaccines in B-cell malignancies and multiple myeloma, with emphasis on immunologic mechanisms, antigen selection, vaccine platforms, and clinical evidence. We further propose a conceptual framework integrating tumor biology, immune context, and combination strategies to guide the rational development of next-generation vaccine therapies. Full article

In this study, we combined computational predictions with experimental validation as a hybrid strategy to explore whether the E protein of tick-borne encephalitis virus (TBEV) possesses autoimmune potential. Using in silico homology searches, we identified two viral epitopes (evglekl and vtgtqgt) within the TBEV E protein that share sequence identity with fragments of the human proteins DNAH7 and CSMD2. Antibodies against these epitopes were detected in the plasma of a subset of patients after natural TBEV infection. Notably, no such antibodies were found in recipients of the Tick-E-Vac vaccine, indicating that the current vaccine does not induce cross-reactive humoral responses to these epitopes. Further computational analysis predicted that these epitopes could be presented by HLA class II molecules (alleles DRB1*09:01 and DRB1*07:01), which are known to be associated with autoimmune pathologies. Molecular dynamics simulations confirmed stable binding of the peptides within the HLA grooves, with favorable binding energies. These findings suggest a possible involvement of T-helper cells in the autoreactive process. Natural TBEV infection can give rise to antibodies against epitopes homologous to human proteins, particularly in genetically predisposed hosts. While such homology alone does not predict the onset of autoimmune disease, it represents a risk factor. Full article

Background: Modified Vaccinia Ankara (MVA) vectors are highly immunogenic vaccine platforms for the delivery of recombinant antigens. Efficient downstream processing is still challenging, particularly because substantial fractions of the virus remain intracellular. While chemical cell lysis that releases MVA particles into the supernatant before clarification can greatly enhance process efficiency and scalability, this step remains insufficiently characterized. Methods: This study assessed the compatibility of ionic, non-ionic, and zwitterionic detergents with the virus as purification target. Polysorbate 20 (Tween 20) was selected as a candidate detergent and evaluated across harvest times of 48–72 h post-infection (hpi) at concentrations of 0.01–0.5% (v/v). Results: The addition of 0.01% to 0.05% Tween 20 at 48 hpi resulted in a twofold increase in supernatant virus within one hour of application. Extended exposure to Tween 20, combined with a 650 mM mixture of NaCl, NaBr, and KCl, promoted virus particle release. However, Tween 20 concentrations above 0.1% reduced MVA infectivity. A filtration cascade using pore sizes of 5 µm and 1.2 µm achieved product yields of 77–83% at 48 hpi and 41–69% at 72 hpi, respectively. Host-cell DNA is an important contaminant during viral vector processing. However, the application of 0.05% (v/v) Tween 20 resulted in a 35% reduction of dsDNA released into the culture supernatant; the nuclei could not be preserved intact under high-salt conditions to avoid the release of cellular DNA. Conclusions: In summary, this comprehensive data demonstrated that non-ionic detergents can be used to induce cell lysis while maintaining infectious activity of enveloped MVA. Full article

mRNA vaccines are a relevant approach in cancer immunotherapy, using messenger RNA to induce immune responses against tumor-associated antigens. In this review, BNT111 and BNT122 are compared as representative off-the-shelf and personalized models. BNT111 is a fixed mRNA vaccine that has demonstrated significant antitumor efficacy against shared melanoma antigens, particularly when combined with immune checkpoint inhibitors. It allows a standardized production via in vitro transcription (IVT) in a cell-free system. Conversely, BNT122 is a personalized vaccine designed to match an individual’s tumor mutations by targeting patient-specific neoantigens to elicit more robust immune responses. It has significant suitability in the adjuvant setting to target minimal residual disease. Despite favorable safety and immunogenicity, the effectiveness of these vaccines is influenced by various factors, including tumor heterogeneity, differences in antigen expression, off-target effects on mRNA-LNP distribution, molecular instability, and complex manufacturing constraints. Neither approach can be directly considered as the definitive optimal vaccine. A comprehensive analysis of their strengths and limitations is vital for a balanced and objective future research direction. Collectively, this emphasizes the need for further improvements in vaccine design and strategies, prioritizing high-quality, safe, and accessible treatments for every cancer-based patient and ensuring their successful integration into healthcare. Full article

Renal cell carcinoma (RCC) is a predominant malignancy of the urinary system, with clear cell renal cell carcinoma (ccRCC) representing 75–85% of clinical cases. Since the early stages are often asymptomatic, nearly 30% of patients present with metastases at diagnosis, which significantly complicates the prognosis. The diverse mechanisms and clinical indications of current strategies, despite recent breakthroughs in immunotherapy, pose a major challenge for systematic application. This review employs the cancer-immunity cycle as a framework to evaluate four critical steps: antigen presentation, T-cell activation, reversal of exhaustion, and immune evasion in the tumor microenvironment. We introduce the major immunotherapy strategies in RCC in this cycle and summarize their clinical position. Combining immune checkpoint inhibitors (ICIs) with tyrosine kinase inhibitors (TKI) has redefined the first-line standard for advanced RCC by addressing both T-cell infiltration barriers and functional suppression. Standalone approaches such as tumor vaccines and cytokines in contrast have shown limited efficacy in advanced settings. In this context, we further propose emerging research directions, such as individualized immunotherapy and multi-target blockade, and point out the relevant biomarkers, offering an integrated perspective of the RCC immune landscape and providing insights for both clinical practice and future research. Full article

Mesothelin (MSLN) is a cell surface glycoprotein with limited expression in normal tissues but frequent overexpression in solid tumors, including gynecological malignancies. This review summarizes the state of the art on the biological role, diagnostic value, prognostic significance, and therapeutic potential of MSLN in ovarian, endometrial, and cervical cancers. Evidence from clinical and experimental studies indicates that MSLN contributes to tumor progression through interactions with CA125, promotion of cell adhesion and peritoneal metastasis, activation of oncogenic signaling pathways, modulation of immune responses, and development of chemoresistance. Elevated MSLN expression has been associated with advanced clinical stage of the disease, platinum resistance, and poorer survival outcomes, particularly in ovarian cancer patients, although prognostic findings remain inconsistent. Circulating soluble MSLN may serve as a minimally invasive biomarker and may improve diagnostic accuracy when combined with established markers. Therapeutic MSLN strategies—antibody-drug conjugates, CAR-T and NK cell therapies, monoclonal antibodies, immunotoxins, vaccines, and checkpoint blockade—provide promising pre-clinical and early clinical results, particularly in resistant or recurrent forms of the disease. Overall, MSLN constitutes a promising target for precision oncology in gynecological cancers, although further clinical studies are required to validate its diagnostic utility and optimize targeted therapeutic approaches. Full article

Cancer vaccines represent a promising strategy in cancer immunotherapy by inducing tumour-specific immune responses. However, their clinical efficacy remains limited due to challenges in antigen selection, including the distinction between self and non-self-antigens, as well as issues related to antigen delivery, immune activation, and tumour immune evasion. Advances in nanotechnology have introduced innovative approaches to improve vaccine stability, targeted delivery, and immunogenicity. Nanoparticle-based platforms, including lipid, polymeric, inorganic nanoparticles, and virus-like particles, enable efficient delivery of tumour antigens and immunostimulatory adjuvants to antigen-presenting cells, thereby enhancing adaptive immune responses. Despite these advances, several translational challenges persist, including immunosuppressive tumour microenvironments, inefficient lymph node targeting, safety concerns, and manufacturing limitations. This review summarizes key nanoparticle platforms used in cancer vaccine development and discusses major barriers to their clinical translation. We also emphasize platform-selection criteria, cargo-dependent carrier design, nanoparticle size constraints, engineering strategies used to improve cytosolic delivery and endosomal escape, and the current clinical pipeline of cancer nanovaccines. Additionally, emerging strategies such as personalized nanovaccines, mRNA vaccine platforms, and combination immunotherapies are highlighted as promising approaches to improve therapeutic efficacy. These advances are expected to accelerate the clinical translation of nanotechnology-enabled cancer vaccines and support the development of next-generation cancer immunotherapies. Full article

Melanoma adjuvant therapy has substantially improved recurrence-free and distant metastasis-free survival in patients with resected high-risk disease, and more recently, these advances have extended to earlier stages. However, important unmet needs remain, including the management of stage IIIA disease, the optimal treatment strategy after relapse on adjuvant therapy, and the identification of biomarkers capable of refining patient selection. This review summarizes recent advances and unresolved questions in the adjuvant and neoadjuvant treatment of melanoma. We discuss novel systemic strategies, including immune checkpoint inhibitor combinations and personalized neoantigen mRNA vaccines, together with the expanding role of neoadjuvant approaches. We also examine prognostic and predictive tools—such as clinicopathologic models, circulating tumor DNA, serum biomarkers, tumor microenvironment features, and gene expression profiling—that may help better define recurrence risk and therapeutic benefit. Current evidence suggests that although modern therapies have changed the natural history of resected melanoma, a substantial proportion of patients are still overtreated or undertreated when treatment decisions are based on stage alone. Future progress will depend on integrating biological risk stratification with clinical staging and optimizing treatment sequencing across adjuvant and neoadjuvant settings. Full article

Background: Effective vaccines are essential to overcome the limitations of livestock immunisation, particularly in low- and middle-income countries (LMICs), where scalable, thermostable, and easy-to-administer solutions are needed. Nanoparticle-based delivery systems, such as the Spontaneous Nanoliposome Antigen Particle (SNAP) technology using CoPoP liposomes, offer a promising alternative for subunit vaccine development, although their performance in large animal species remains poorly characterised. CoPoP enables the rapid non-covalent multimeric display of His-tagged protein antigens combined with immunomodulators on liposomes incorporating cobalt porphyrin–phospholipid (CoPoP). Objective: To evaluate the immunogenicity of CoPoP-based liposomes delivering the Theileria parva p67C antigen in cattle and compare their performance in murine models. Methods: Cattle and mice were immunised with p67C formulated in CoPoP liposomes incorporating QS-21 and/or PHAD immunomodulators. Humoral and cellular responses were assessed. Parallel in vitro stimulation of bovine PBMC with Quil-A was used to investigate the mechanistic effects of saponins on bovine cells. Results: CoPoP liposome formulations did not improve p67C immunogenicity in cattle, with antibody responses at least two-fold lower than previously reported results and no detectable cellular responses. In contrast, the same platform induced up to 2000-fold higher antibody titres in mice. This disparity is likely driven by differences in antigen dose relative to body mass, tissue architecture, lymphatic accessibility, and innate immune signalling differences. PHAD-mediated TLR4 activation appeared less effective in cattle, whereas QS-21 induced a broader immune activation, likely through conserved inflammasome pathways. Despite limited immunogenicity, antigen presentation by CoPoP liposomes was preserved. Conclusions: SNAP-based CoPoP liposomes showed strong immunogenicity in mice but limited efficacy in cattle, highlighting the challenges of cross-species translation. Optimisation of antigen dose and adjuvant selection for the targeted species is required, with QS-21 representing a more promising candidate than the TLR4 agonist. The scalability and versatility of SNAP technology support its continued development for multivalent livestock vaccines. Full article

Background/Objectives: Vaccine development pipelines are forward-looking indicators of public health preparedness, reflecting the capacity to address unmet medical needs and emerging threats. This descriptive analysis aims to characterise the 2025 clinical-stage pipeline of infectious disease vaccines and prophylactic monoclonal antibody candidates developed by Vaccines Europe member companies, and to describe how pipeline characteristics address evolving public health priorities. Methods: A descriptive analysis was conducted using publicly available data compiled in the Vaccines Europe Pipeline Review 2025, with validation by participating companies. Candidates in clinical development or regulatory review were classified using a standardised framework by pathogen/disease, target population, public health priority, and technologies. Results: The Vaccines Europe member company pipeline comprises 91 candidates across clinical development phases, 19% of which are in Phase III and 7% undergoing regulatory review. This pipeline is predominantly targeting respiratory pathogens (75%), with a strong life-course focus (85% evaluated in adults and/or older adults), and sustained activity in bacterial pathogens relevant to antimicrobial resistance. Notably, 41% of candidates were classified as addressing diseases, disease combinations, or indications for which no licenced preventive product exists. This category includes candidates targeting diseases without a preventive solution, as well as novel combination vaccines and therapeutic approaches in areas where individual components or preventive vaccines are already available. This captures vaccines candidates in different stages of development, not necessarily first-in-disease innovation. The pipeline shows broad technological diversity (12 technologies), dominated by RNA approaches and multivalent candidates, with growing focus on climate-sensitive, zoonotic, and pandemic-prone pathogens. Conclusions: Within the pipeline of Vaccines Europe member companies, this analysis describes development activity oriented toward broader prevention, platform-based approaches, and preparedness-relevant targets. As a structured and recurring annual assessment, the Vaccines Europe Pipeline Review supports horizon scanning and evidence-based dialogue between industry and vaccine ecosystem stakeholders. In order to maximise the impact of vaccine development pipelines to public health, predictable investment, streamlined trial and regulatory pathways, strong surveillance, and real-world data systems, coordinated decision-making is required to enable timely and equitable access, and complementary incentive and procurement reforms. Full article

Background/Objectives: Recurrent influenza epidemics impose a severe global burden, with conventional vaccines constrained by production time lags and rapid viral mutation. This study aims to explore a novel influenza mRNA vaccine design that balances conserved and mutable antigen regions. By combining hemagglutinin (HA) and neuraminidase (NA) into a dual-target approach, the objective is to simultaneously block viral entry and inhibit progeny release, potentially establishing a proposed “front-blockade, rear-containment” dual protective barrier against multiple H1N1 strains. Methods: We engineered a dual-target tandem mRNA vaccine linking mutated HA with conserved NA, with strategic amino acid mutations introduced into key antigenic sites within the HA head domain. Vaccine efficacy was evaluated in a mouse model. Humoral immunity was assessed by measuring antigen-specific antibody titers, and cellular immunity was evaluated via ELISpot assay. Protective capacity was determined through lethal challenge experiments using diverse H1N1 viral strains. Results: The vaccine successfully expressed the HA-NA tandem antigen at 130 kDa, and the in vitro-expressed antigen exhibited normal neuraminidase activity. Preliminary evidence supported the dual-target concept in model mice: hemagglutination-inhibiting and micro-neutralizing antibodies targeting HA were detected, and serum neuraminidase-inhibiting activity was also observed. In addition to triggering potent cellular immune responses, the vaccine offered total protection against lethal doses of various H1N1 variants. Conclusions: This study suggests a promising dual-target strategy that harmonizes antigen conservation and mutation while potentially establishing a synergistic front-blockade and rear-containment defense. The approach offers a viable pathway for developing improved H1N1 influenza vaccines. Full article

Background/Objectives: Transitions to new vaccines or antigen schedules represent complex system changes requiring coordinated governance, reliable data systems, domestic financing, and multisectoral collaboration. In 2025, African countries were moving toward a switch from separate pentavalent and inactivated poliovirus vaccines to the combined hexavalent vaccine. This project report describes the Hexavalent Vaccine Switch Early Adopters Workshop in Dakar, Senegal, which included ten African countries, and its implications for future vaccine introductions. Methods: We conducted a practice analysis drawing on structured documentation of plenary presentations, country case studies, interactive problem-solving sessions, and national roadmap exercises. A thematic framework aligned to ten process points for the hexa switch guided synthesis. Results: Countries reported shared system vulnerabilities, including coexistence risks of legacy and new vaccine stocks, inconsistent data completeness, under-resourced vaccine safety surveillance, and financing uncertainties. Early adopter countries demonstrated operational feasibility, logistical efficiencies, and opportunities for reducing injection burden. Outputs included a Health System Adaptation Checklist, a Switch Risk Mitigation Catalog, and 12-month national roadmaps. Conclusions: Regional peer-learning mechanisms can accelerate decision-making, improve operational quality, and strengthen accountability for vaccine introductions. Structured cross-country collaborations can transform a product switch into a scalable system-strengthening opportunity. Full article

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy, with rising incidence and a 5-year survival rate of 13%. Late presentation, early metastasis, and intrinsic resistance constrain the efficacy of cytotoxic chemotherapy, which remains the backbone of PDAC treatment, with only modest survival gains and resistance nearly universal. Although KRAS mutations dominate tumour biology (~90% of cases), PDAC is a heterogeneous disease with distinct molecular subtypes that confer differential therapeutic vulnerabilities. Advances in comprehensive molecular profiling have catalysed a paradigm shift toward precision oncology in PDAC. In KRAS-mutant PDAC, mutation-specific inhibitors have established proof-of-concept, particularly in KRAS G12C disease, while next-generation approaches including KRAS G12D inhibitors, RAS-“ON” inhibitors, proteolysis-targeting chimeras (PROTACs), and KRAS-targeted vaccine strategies are expanding the therapeutic landscape. Combination strategies targeting upstream and downstream effectors of the RAS–MAPK pathway are also being explored to enhance the depth and durability of response. In parallel, KRAS-wild-type PDAC has emerged as a molecularly distinct subgroup enriched for rare but actionable alternative oncogenic fusion drivers including NRG1, NTRK, RET, ALK, and FGFR. Additional molecularly directed strategies targeting HER2 alterations, BRAF mutations, EGFR-dependent signalling, and tumour-selectively exposed surface antigens such as CLDN18.2 are under investigation across PDAC irrespective of KRAS mutation status. Synthetic lethal approaches, including targeting the PRMT5/CDKN2A/MTAP axis, represent a further emerging therapeutic strategy. Germline homologous recombination repair defects, particularly involving BRCA1/2 and PALB2, further define clinically important subsets with sensitivity to platinum chemotherapy and PARP inhibition. This review summarises current and emerging targeted and molecularly directed therapeutic strategies in PDAC, emphasising the importance of molecular stratification and recent advances shaping precision oncology in this historically treatment-refractory disease. Full article

Background/Objectives: The COVID-19 pandemic disrupted routine immunisation globally. Saudi Arabia presents a unique epidemiological context for measles, combining high vaccination coverage with mass pilgrimages and a large expatriate workforce. This study examined measles incidence trends, vaccination coverage, and demographic and geographic burden distribution in Saudi Arabia (2015–2024), with comparative analysis against GCC countries, the Eastern Mediterranean Region (EMR), and global data. Methods: Annual incidence and vaccination coverage data were obtained from the WHO Global Health Observatory and WHO/UNICEF WUENIC; monthly, regional, age- and nationality-stratified data from the Saudi Ministry of Health Annual Statistical Book (2015–2024). Incidence was expressed per 1,000,000 population across three epochs: pre-COVID-19 (2015–2019), pandemic disruption (2020–2021), and post-COVID-19 rebound (2022–2024). Descriptive analyses included period means, percentage changes, rate ratios, and rate differences. Results: Pre-COVID-19 incidence (mean 19.7/1,000,000) remained below EMR and global averages. The pandemic produced near-complete suppression (−96.6% to 1.1/1,000,000 in 2020), exceeding global (−82.2%) and EMR (−61.2%) declines. A marked rebound occurred in 2023 (67.8/1,000,000), surpassing the pre-pandemic peak despite MCV1/MCV2 coverage above 96%. Non-Saudi nationals bore disproportionate burden in 2021 (20.7 vs. 1.1/1,000,000) and 2023 (70.4 vs. 64.8/1,000,000). Children under 15 accounted for 71.6–90.6% of annual cases, with the 5–<15-year group’s contribution rising from 12.7% (pre-COVID mean) to 27.7% in 2024. Geographic burden shifted annually with no consistently dominant region. Conclusions: Saudi Arabia’s post-pandemic rebound despite high national coverage implicates sub-population susceptibility gaps among non-national residents and school-age children, alongside importation risks from mass pilgrimage. Targeted strategies addressing demographic and geographic heterogeneity are essential to meet WHO 2030 elimination targets. Full article

Background/Objectives: Several subunit vaccines for tuberculosis (TB), such as MVA85A and H4:IC31, have not demonstrated ideal protective efficacy in clinical trials, which may be attributed to their limited antigenic profile and lack of effective latency-associated antigens. In this study, we combined bioinformatics with experimental validation to screen for latency-associated antigens that have immune-protective effects. Methods: Highly expressed antigens were identified from models related to latent infections, such as hypoxia and nutritional starvation. Their physicochemical properties and immunogenicity were predicted using online tools such as Expasy-ProParam, IEBD, and VaxiJen. The immunogenicity of these antigens was then evaluated in multiple mycobacterium infection models. Finally, a systematic evaluation of the immune response and protective effects induced by the candidate antigens was performed in a mouse model using intracellular cytokine detection, mycobacterium growth inhibition assays (MGIAs), antibody-dependent cellular phagocytosis (ADCP), and a latent tuberculosis infection (LTBI) mouse model. Results: The antigen Rv2656c is highly expressed in the nutritional starvation model and demonstrates strong immunogenicity in both infected humans and cattle. Moreover, Rv2656c exerted a significant inhibitory effect against Mycobacterium tuberculosis (M. tuberculosis) and Mycobacterium avium (M. avium) infections in MGIA. The humoral immune response elicited by Rv2656c enhanced the phagocytosis and killing of Mycobacteria by macrophages in vitro. Furthermore, in a mouse model of LTBI established using the attenuated M. tuberculosis H37Ra strain, treatment with Rv2656c significantly decreased the bacterial load in the lungs of the mice. Conclusions: Latency-associated Rv2656c may serve as an immune-protective antigen, offering potential for the development of novel multi-stage antigen subunit vaccine against TB. Full article