Search Results (1,054)

Background: Despite universal infant hepatitis B virus (HBV) vaccination, declining circulating anti-HBs levels are increasingly observed in young healthcare professionals, a high-risk group for occupational exposure. Although several studies have evaluated HBV antibody persistence in healthcare workers, data specifically addressing newly incorporated medical residents in the Spanish context remain limited. This study evaluated baseline anti-HBs levels and serological response to a vaccination booster dose in medical residents at a Spanish tertiary hospital. Methods: A retrospective longitudinal observational study was conducted among medical residents attending the Preventive Medicine Service of Hospital Universitario San Cecilio (Granada, Spain) between 2021 and 2024. Anti-HBs antibody titers were obtained at baseline and ≥10 mIU/mL were considered the conventional protective threshold. Residents with anti-HBs < 10 mIU/mL received an Engerix-B booster followed by repeat serology. Demographic and occupational variables were analyzed. Measles serostatus was collected for comparisons. Results: A total of 275 residents were included (mean age 25.4 years, SD = 2.3 years; 64% females). Baseline serology showed anti-HBs levels < 10 mIU/mL in 53.1% of participants. Lower baseline anti-HBs levels were associated with younger age (adjusted OR = 0.75; 95% CI: 0.64–0.88) and earlier residency year (R1–R2) (adjusted OR = 0.28; 95% CI: 0.13–0.61). Among 116 residents receiving a booster, 94.8% achieved anti-HBs ≥ 10 mIU/mL after booster administration. Measles serology was negative in 54.6% of participants. Conclusions: More than half of newly incorporated medical residents had anti-HBs levels below the conventional protective threshold (10 mIU/mL), yet almost all demonstrated a strong anamnestic response, supporting the persistence of immunological memory despite reduced circulating antibody concentrations. Systematic baseline screening combined with targeted booster vaccination appears to be an effective strategy to ensure occupational protection. Further research incorporating cellular immunity markers may refine future vaccination policies and booster strategies. Full article

People living with HIV (PLWH) receiving effective antiretroviral therapy (ART) continue to exhibit chronic immune activation and systemic inflammation despite virological suppression. The viral envelope glycoprotein gp120, which binds the CD4 receptor and mediates viral entry, has been implicated in pro-inflammatory and pro-apoptotic effects in neuronal and endothelial cells. Although gp120 is expressed on the viral surface, its oligomeric structure and its ability to form immune complexes with circulating antibodies may reduce the sensitivity of standard detection assays in serum. Soluble gp120 has been associated with increased levels of pro-inflammatory cytokines, including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), as well as chemokines. These mediators may contribute to blood–brain barrier dysfunction, endothelial injury, vascular smooth muscle alterations, and subsequent neurodegenerative and cardiovascular complications. Importantly, gp120 shedding may persist due to viral reservoirs and intermittent reactivation, even during ART. Fostemsavir inhibits the interaction between gp120 and CD4, preventing viral entry and potentially limiting gp120-mediated pathogenic effects. Beyond antiviral activity, this mechanism suggests a potential role in attenuating gp120-mediated inflammation. This review discusses the biological effects of gp120 and the rationale for targeting it therapeutically in PLWH. Full article

This study aimed to elucidate the key characteristics of the humoral immune response and the tissue distribution of specific antibody-secreting cells (ASCs) in Nile tilapia (Oreochromis niloticus). A specific immune model was established by immunizing fish with human IgG. Lymphocytes were isolated from the head kidney, spleen, and peripheral blood and subjected to antigen stimulation in vitro. The MTT assay, reflecting cell metabolic activity and viability, identified the optimal culture conditions as a cell concentration of 2.5 × 10⁶ cells/mL, an antigen concentration of 2 μg/mL, and a culture duration of 72 h. Under these conditions, peripheral blood lymphocytes exhibited the most increase in metabolic activity, followed by head kidney lymphocytes, while splenic lymphocytes showed no significant response. Subsequent dynamic monitoring of antibody-secreting cells (ASCs) using ELISPOT revealed that, in the absence of antigen stimulation, ASC numbers from all three tissues declined over time. Notably, head kidney ASCs retained approximately 50% of their initial number by day 5, whereas ASCs in peripheral blood and spleen decayed to barely detectable or completely undetectable levels, respectively. These findings suggest that the head kidney may serve as a primary site for ASC persistence during the effector phase, potentially contributing to sustained humoral immunity. Although antigen stimulation did not induce significant ASC expansion, it significantly slowed their decay rate (p < 0.05), indicating an antigen-dependent maintenance role. ELISA detection of antibody levels in the culture supernatants showed a consistent trend with the ELISPOT results, further confirming the sustained functional support of antigen for ASCs. Additionally, LPS stimulation experiments demonstrated that all three tissues contained plasmablasts activatable by non-specific stimuli, with peripheral blood showing the highest proliferation fold (4–6 times). In conclusion, this study provides insights into the tissue-specific distribution, in vitro persistence, and antigen-dependent maintenance of ASCs in Nile tilapia, providing insights into the cellular basis that may contribute to humoral immune memory and laying a theoretical foundation for the rational design and application of tilapia vaccines. Full article

Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disease (NMD) caused by loss-of-function mutations in the DMD gene. RNA-based therapies, especially antisense oligonucleotides (ASO)-mediated exon skipping and adenosine deaminase acting on RNA (ADAR)-guided RNA editing, have emerged as complementary approaches that modulate pre-mRNA splicing or correct transcripts without altering genomic DNA. Current phosphorodiamidate morpholino oligomer (PMO) drugs targeting exons 51, 53, and 45 provide mutation-class-specific benefit. At the same time, next-generation delivery strategies (e.g., peptide-conjugated PMOs (PPMOs), antibody–oligonucleotide conjugates (AOC), and endosomal-escape vehicles) aim to improve skeletal, cardiac, and diaphragm exposure. In parallel, RNA editing strategies offer a route to correct select nonsense or missense variants at the base level and may, in principle, restore near-native dystrophin expression. Meaningful translation of these modalities requires predictive large-animal models. A genome-edited microminipig (MMP) bearing DMD exon-23 mutations faithfully recapitulates hallmark features of human DMD. That includes early locomotor deficits, elevated serum creatine kinase (CK) and cardiac troponin T, progressive myocardial fibrosis, and a decline in left-ventricular ejection fraction (LVEF), while maintaining a manageable lifespan of approximately 30 months suitable for long-term studies. In particular, the MMP model provides a practical platform for addressing the persistent challenge of efficient therapeutic delivery to the heart and diaphragm through longitudinal dosing, imaging, and biopsy. In this review, we synthesize clinical progress in exon skipping, outline the promise of RNA editing, and integrate recent insights from Duchenne muscular dystrophy model for microminipigs (DMD-MMPs) as an advanced surrogate for preclinical development and translational evaluation. Full article

Background/Objectives: Protein–protein interactions (PPIs) involving oncogenic drivers remain among the most intractable targets in cancer biology due to their dynamic conformations and limited accessibility to conventional small molecules. Although antibodies and inhibitors have achieved clinical success against targets such as PD-1/PD-L1 and MYC, challenges persist related to tissue penetration, intracellular delivery, resistance, and incomplete blockade of key interface hotspots. The objective of this study is to develop an integrated computational framework for systematically designing hotspot-conditioned de novo miniprotein binders to target these interfaces. Methods: We present DesignForge, a computational protein design pipeline that integrates energetic hotspot identification, generative backbone design, sequence optimization, and structural confidence evaluation. The framework combines hotspot mapping using an open force-field-based energetic analysis module with generative backbone sampling using BindCraft, sequence optimization using ProteinMPNN, and structural validation using AlphaFold2. This in silico pipeline was applied to three representative oncogenic interfaces: PD-1/PD-L1, MYC/MAX, and KRAS/RAF. Results: Computationally generated designs exhibited high predicted structural confidence, favorable interface energetics, and consistent engagement of identified hotspot residues across targets. AlphaFold2-Multimer structural modeling indicated that the candidate PD-1 mimetic scaffolds, MYC/MAX interface binders, and KRAS interaction candidates can adopt conformations compatible with the target interfaces. Energetic contact analysis further supported predicted engagement of key hotspot residues. These findings support the computational feasibility of hotspot-conditioned binder generation using a unified design workflow. Conclusions: DesignForge provides a reproducible computational framework for hotspot-guided de novo protein binder design targeting oncogenic protein–protein interfaces. The designs reported here represent computational predictions derived from structural modeling and energetic analysis. Experimental biochemical and cellular validation will be required to determine the functional activity of the proposed binders. Full article

Background: Porcine epidemic diarrhoea virus (PEDV) is a highly contagious pathogen causing severe diarrhoea and high mortality in neonatal piglets. Methods: In this study, consensus sequences encoding the N-terminal domain of spike subunit 1 (S1-NTD) and nucleocapsid (N) protein of PEDV were cloned into a eukaryotic expression vector pJHL204 and transformed into an attenuated Salmonella Typhimurium strain JOL2500. Antigen expression was confirmed by Western blot and immunofluorescence analyses. The recombinant strains were evaluated in vivo for safety, persistence, and immunogenicity. Immunogenicity was characterised by measuring antibody response, virus neutralising assays, cytokine profiling, and flow cytometric analysis of T cell subpopulation. Protective efficacy against salmonellosis in dams and passive transfer of neutralising antibodies to suckling mice were evaluated. Results: Vaccinated mice exhibited no adverse effects or bacterial persistence in major organs, confirming the vaccine’s safety. Immunisation elicited robust PEDV- and Salmonella-specific humoral and cell-mediated immune responses. Upon Salmonella challenge, vaccinated mice showed significantly reduced bacterial loads in splenic tissues. Furthermore, vaccinated dams and their offspring induced detectable anti-PEDV neutralising antibodies, indicating successful passive antibody transfer. Conclusion: Our findings indicate that the designed vaccine constructs provide a promising platform for inducing multifaceted immuno-protectivity against PEDV and salmonellosis. Full article

Next-generation sequencing (NGS) and antisense oligonucleotide (ASO) technologies are converging to transform the diagnosis and treatment of rare monogenic disorders. NGS enables comprehensive, single-test molecular diagnoses through targeted panels, whole-exome sequencing, and whole-genome sequencing, which together reveal pathogenic variants across coding, intronic, and structural domains. Integration with transcriptomic analyses, including RNA sequencing, further refines genotype–phenotype correlations and identifies splicing aberrations amenable to correction by ASOs. Therapeutic advances now span RNase H1-dependent gapmers for transcript knockdown, splice-modulating phosphorodiamidate morpholino oligomers (PMOs), and peptide/antibody-conjugated PMOs that enhance muscle and cardiac delivery. These platforms underpin the rise in N-of-1 ASO therapies—customized drugs developed for individual patients with unique pathogenic variants. Landmark cases such as Milasen and Atipeksen illustrate the clinical feasibility and ethical complexities of personalized RNA therapeutics, while updated FDA guidance supports expedited, patient-specific investigational pathways. Despite progress, challenges persist in delivery efficiency, long-term efficacy, and equitable access. Emerging approaches—including long-read sequencing, AI-driven oligo design, and improved delivery—promise to extend ASO precision and reach. This review synthesizes current advances linking genomic diagnosis to individualized RNA-targeted interventions, outlining how integrated NGS-ASO pipelines are reshaping the therapeutic landscape for rare genetic diseases. Full article

Bovine leukemia virus (BLV) is an oncogenic deltaretrovirus that infects B cells, and its possible presence in humans has garnered increasing attention. This study included 58 participants: 11 with B-cell precursor acute lymphoblastic leukemia (B-ALL, cases) and 47 healthy individuals (controls). Researchers assessed anti-gp51 antibodies and BLV proviral DNA in bone marrow and blood samples. Seropositivity was observed only in the B-ALL group (18.2%; 2/11), while all controls were seronegative. Quantitative PCR targeting the pol gene detected proviral DNA in 74.1% of samples, with similar detection rates between cases and controls. Although proviral load was higher in controls, this difference did not reach statistical significance. Conventional and nested PCR for other viral genes revealed a differential pattern: amplification of the tax gene was significantly associated with B-ALL, whereas gag and env were not. Bayesian Chow–Liu network analyses identified dependencies among viral genes and suggested that contextual factors, such as fieldwork, may influence the association between molecular positivity and B-ALL. Sequence analyses showed that the detected BLV strains clustered with previously reported bovine and human sequences from Colombia, all within genotype 1. These findings support human exposure to BLV and raise important questions about its persistence and potential connections to hematological diseases in humans. Full article

Pigeon Newcastle disease poses a persistent threat to the global pigeon industry, underscoring the need for effective vaccination strategies. While both inactivated and DNA vaccines offer distinct advantages, the immunogenicity of a combined heterologous regimen remains underexplored. This study evaluated and compared three immunization strategies in pigeons: a DNA vaccine encoding the NDV F protein fused with chicken IL-18, an inactivated vaccine from a local virulent strain, and a DNA prime-inactivated boost regimen. The preparation workflows for both vaccine platforms are described in detail to provide methodological context for the immunological comparison. Critically, the prime–boost regimen elicited significantly higher hemagglutination inhibition (HI) antibody titers than either vaccine administered alone, demonstrating a clear synergistic effect. These findings highlight the complementary roles of the two platforms and provide a strong immunological rationale for further evaluation of this sequential strategy. Future studies incorporating viral challenge experiments and long-term immune monitoring are needed to determine whether the enhanced HI antibody response translates into protective efficacy under field conditions. Full article

Acute and chronic wounds are a major clinical burden, with persistent inflammation, impaired fibroblast function, defective angiogenesis, and disordered extracellular matrix deposition. The translational potential of existing in vitro models is limited by their poor durability and physiological relevance. The present paper aims to develop a robust in vitro organotypic model to simulate the early phases of both acute and chronic wounds and to validate it by testing the biocompatibility of clinically available wound dressings. Human fibroblasts and vascular endothelial cell lines were cultured at a ratio of 1:1 for 48 h, either on uncoated tissue culture plastic or on tissue culture plastic coated with a synthetic substrate (PhenoDrive-Y) that biomimics the extracellular matrix and promotes cell organization into tissue-like structures on a 2D plane (i.e., angiogenesis sprouting and fibroblast organization around it). Wound conditions were then created by damaging the formed structures using a conventional scratch procedure and introducing U937 human macrophage cells to the model to simulate either the onset of an acute wound or that of a chronic wound through the simultaneous spiking of the culture with relevant cytokines, i.e., IL-6 and TNF-α. The formation of new tissue-like structures in the scratch area was quantified by the extent of scratch closure after a further 24 h of incubation. Morphological analysis of wound healing was performed by light microscopy, while angiogenesis was assessed by CD31 immunostaining by confocal microscopy. The deposition of components of the extracellular matrix was determined both qualitatively and quantitatively by Picrosirius Red staining for collagen production and by Alcian Blue staining for glycosoaminoglycan synthesis on the adhering cells and their supernatants. Macrophage polarization into either M1 or M2 phenotype was studied by immunostaining with iNOS (M1) and CD206 (M2) antibodies by confocal microscopy. The model was validated by studying the gap closure areas in simulated acute and chronic wound-like conditions when incubated with clinically available wound dressings, N-A Ultra and Kaltostat. PhenoDrive-Y allowed the formation of tissue-like structures on the 2D tissue culture plane as opposed to the formation of cell monolayers on the uncoated tissue culture plastic. Upon mechanical damage, cell migration was significantly different; uncoated control co-cultures achieved complete closure as an indistinct monolayer by 24 h, while the organotypic wound models showed a slower percentage of damage closure. A further delay in the closure of the damaged area was observed when chronic wound-like conditions were simulated. Angiogenesis in chronic wound conditions was considerably impaired compared to the acute conditions. The analysis of the extracellular matrix component synthesis, specifically collagen and polysaccharides, revealed the deposition of dense, organized collagen fibers in the acute wound model, in contrast to the thin, fragmented collagen fibers and intracellular polysaccharides observed under chronic wound-like conditions. This corresponded to a statistically significant increase in the levels of both collagen and polysaccharides detected as soluble molecules in the supernatants. Macrophage polarization showed no statistically significant differences in the acute and chronic wound models, though iNOS did significantly decrease after N-A application in acute and chronic models. However, acute wound-like conditions showed a restoration of the vascularized tissue-like structures after treatment with these types of dressings, albeit through different organizational pathways, whereas only minimal improvement was noted under chronic wound conditions, particularly in the case of the N-A dressing. The organotypic dermis model for the onsets of acute and chronic wounds emerges as a highly versatile tool to understand healing mechanisms in the absence or presence of co-morbidities and to assess the biocompatibility of wound dressings as well as the safety, efficacy and dosage of drugs. Full article

Background and Objectives: High-grade serous ovarian carcinoma (HGSC) is characterized by aggressive tumor behavior, frequent recurrence, and limited long-term survival. Despite the established clinicopathological prognostic factors, significant heterogeneity in clinical outcomes persists, highlighting the need for biologically relevant molecular biomarkers. HER3 and folate receptor alpha (FOLR1) have promising prognostic biomarkers in ovarian cancer; however, the combined biological and prognostic impact of these two molecules has not yet been clearly demonstrated. Materials and Methods: This retrospective observational study included 66 patients with histopathologically confirmed HGSC. The immunohistochemical expression of HER3 and FOLR1 was evaluated using a standardized immunoreactivity scoring system. Associations with clinicopathological features were analyzed, and survival outcomes were analyzed using Kaplan–Meier analysis and Cox proportional hazards regression models. Results: High HER3 expression was significantly associated with distant metastasis and was identified as an independent adverse prognostic factor for both overall survival (OS) and progression-free survival (PFS). FOLR1 expression was associated with OS in univariate analysis, but did not retain independent prognostic significance in multivariate models. A moderate yet statistically significant positive correlation between HER3 and FOLR1 expression was observed, suggesting a potential association between proliferative signaling and metabolic pathways that may warrant further mechanistic investigation. Conclusions: Our findings demonstrate that HER3 is a robust prognostic biomarker in HGSC and support a biologically relevant HER3–FOLR1 interaction contributing to tumor aggressiveness. These results provide a translational rationale for combined biomarker assessment and for the development of HER3- and FOLR1-targeted therapeutic strategies, particularly antibody–drug conjugates, for HGSC. Full article

Background/Objectives: Real-world persistence of traditional oral migraine preventive medications is low in routine care. Prior large claims-based analyses demonstrated early discontinuation of oral prophylaxis, but such datasets neither included modern preventive options such as monoclonal antibodies (mAB) against calcitonin-gene-related peptide (CGRP), nor were able to capture clinically validated reasons for discontinuation. The primary aim was to compare real-world treatment persistence and discontinuation reasons due to adverse drug reactions (ADRs) or insufficient efficacy among three preventive therapy classes: subcutaneous CGRP mAB and oral high- (HEVP) and low-evidence preventive medications (LEVP). A secondary aim was to examine persistence patterns of individual substances within the HEVP cohort. Methods: This exploratory observational study used depersonalized real-world data from the German Pain e-Registry (GPeR), a national multicenter clinical registry. Persistence trajectories were evaluated over six months, together with cumulative proportions of ADR-related and inefficacy-related discontinuations. Pairwise comparisons across the three cohorts based on chi-square analyses, odds ratios, relative risks, effect sizes, and numbers needed to harm. Results: At six months, persistence was highest for CGRP monoclonal antibodies at 89.4%, compared with 43.0% for LEVP and 34.0% for HEVP (all p < 0.001). ADR-related discontinuation occurred in 7.0% with CGRP vs. 35.7/44.5% with LEVP/HEVP, and discontinuations due to insufficient efficacy occurred in 3.6% with CGRP vs. 21.3/21.5% with LEVP/HEVP, without influence of sex or migraine frequency. Substance-level analysis within HEVP showed the steepest early attrition for tricyclic antidepressants, followed by beta-blockers, with comparatively more favorable though still suboptimal persistence for topiramate and flunarizine. Conclusions: Real-world treatment persistence is markedly higher with CGRP mAB than with HEVP/LEVP. Oral preventives show high discontinuation rates due to both ADR and insufficient efficacy, indicating substantial limitations in real-world applicability. These findings highlight the clinical relevance of a modern mechanism-based migraine prevention with CGRP mAB. Full article

Background: Adolescent migraine is highly prevalent and associated with substantial functional and psychosocial burden. Conventional oral preventives are widely used off-label with limited pediatric efficacy and frequent tolerability problems. Real-world data on calcitonin gene-related peptide (CGRP) monoclonal antibodies in adolescents are scarce. Methods: We conducted an exploratory, retrospective cohort analysis of depersonalized routine-care data from adolescents with migraine in the German Pain e-Registry. Patients were eligible if they had at least one 6-month episode with high-evidence conventional oral preventives (HECP) and one 6-month episode with a CGRP monoclonal antibody (CGRP-mAb), each with baseline and follow-up documentation, enabling intra-individual descriptive comparisons. The primary endpoint was a pragmatic composite of 6-month treatment persistence and ≥50% reduction in monthly migraine days (MMD). Secondary outcomes included MMD, MMD with acute medication (MMDAM), migraine-related sick-leave days (MMSLD), disability (MIDAS), and patient-reported psychosocial outcomes. Results: A total of 422 adolescents contributed 1448 HECP and 422 CGRP-mAb episodes. Premature discontinuation occurred in 68.8% (HECP) and 11.9% (CGRP-mAb) of episodes; corresponding 6-month persistence was 30.6% and 88.2%, respectively. Mean MMD decreased from 11.7 to 9.4 during HECP episodes and from 11.6 to 4.4 during CGRP-mAb episodes. A ≥50% MMD reduction occurred in 25.4% (HECP) and 70.9% (CGRP-mAb) of episodes; the composite endpoint was met in 23.7% and 69.9%, respectively. CGRP-mAb episodes were associated with numerically larger improvements across secondary outcomes. Conclusions: In this high-burden adolescent cohort, CGRP-mAb treatment episodes were associated with higher persistence and broader improvements than prior conventional preventive episodes. Given the retrospective, non-randomized, sequential design, these findings are hypothesis-generating and do not constitute evidence of comparative effectiveness. Controlled pediatric trials and long-term safety studies are warranted. Full article

Background and Objectives: Post-COVID-19 syndrome (PCS), characterized by persistent fatigue, can develop after a SARS-CoV-2 infection. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, post-infectious condition marked by severe fatigue and post-exertional malaise. This study aimed to determine the incidence and characteristics of PCS and ME/CFS in a cohort of hospital employees (HEs) with SARS-CoV-2 infections. Materials and Methods: All HEs who tested SARS-CoV-2-positive between March 2020 and May 2021 who later reported persistent fatigue were invited for an assessment from July to December 2022. Canadian Consensus Criteria were used for the diagnosis of ME/CFS. Assessments included the Montreal Cognitive Assessment (MoCA), and determination of coagulation factors, Epstein–Barr virus (EBV) antibodies and autoantibodies (AABs) against G-protein-coupled receptors (GPCRs). Results: Of the 221 HEs, 11.8% (95% confidence interval (CI95%) 7.8–16.8, 26/221) still reported persistent fatigue and 3.2% (CI95% 1.3–6.4, 7/221) were diagnosed with ME/CFS. In total, 19 HEs (median age 51.0 years, 89.4% female, 63.1% possible or confirmed nosocomial infection) participated in our assessment. In 42.1% (8/19) MoCA results were below normal. Laboratory values showed increased GPCR AABs in 66.6% (12/18), possible EBV reactivation in 86.7% (13/15) and coagulation parameters suggesting inflammatory processes in 38.9% (7/18). Conclusions: Our study was able to determine lower-bound incidences of PCS with fatigue and ME/CFS and demonstrated a diagnostic pathway for HEs following SARS-CoV-2 infections. Possible EBV reactivation, increased GPCR AABs and potential coagulation cascade activation may play a pathogenic role. Full article

Background/Objectives: Head and neck squamous cell carcinoma (HNSCC) affects over 600,000 individuals worldwide each year, and its incidence continues to rise. There is a growing need for novel therapeutic strategies that achieve high antitumor efficacy while minimizing functional impairment. We developed a novel approach to enhance intracellular delivery of immunotoxins (ITs) by combining a photosensitizer under illumination. This method, termed intelligent Targeted Anti-body Phototherapy (iTAP), utilizes light as a spatiotemporal trigger to promote the cytoplasmic release of toxins. In the present study, we investigated the in vivo therapeutic efficacy of iTAP using an EGFR-targeted IT composed of cetuximab conjugated to saporin (IT-Cmab), administered in combination with the clinically used photodynamic therapy (PDT) photosensitizer NPe6, in a xenograft mouse model. Methods: Sa3 cells were implanted subcutaneously into the right hind limb of nude mice. Mice were randomized into four groups (n = 5): (i) iTAP (IT-Cmab plus NPe6), (ii) IT-Cmab alone, (iii) NPe6 alone, and (iv) saline control. Treatment was initiated once tumors exceeded 40 mm³. Mice received intraperitoneal IT-Cmab (0.5 mg/kg), followed 72 h later by intravenous NPe6 (5 mg/kg). Tumors were irradiated 3–4 h later using a custom LED device (670 nm, 262 mW/cm², 30 J/cm²). Tumor volume and body weight were monitored over time, and antitumor effects were analyzed using a linear mixed-effects model. Results: iTAP treatment produced the earliest and most pronounced inhibition of tumor growth among the four groups. Significant suppression was observed from day 9 and persisted throughout the study. IT-Cmab alone showed a moderate but sustained antitumor effect with a later onset, whereas NPe6-mediated PDT exhibited only a delayed and weaker response. On the final day, median tumor volumes showed substantial reductions relative to the Control group (601%), with decreases of 41% in PDT (357%), 55% in IT-Cmab (271%), and 70% in iTAP (178%). Overall, iTAP demonstrated the strongest and most durable therapeutic efficacy in vivo. Conclusions: These findings indicate that iTAP represents a promising therapeutic strategy for HNSCC. Full article