Biopharma Technology (United Kingdom)

Immune responses naturally decline with age in the elderly; this process is named immunosenescence. The risks for adverse events (AEs) can increase, decrease, or be uncorrelated with increasing age. Safety signals associated with vaccines can be detected within the Vaccine Adverse Event Reporting System (VAERS). Herein, VAERS was retrospectively examined for safety signals associated with the elderly. In general, common AEs include normal immune responses and also injection site-related AEs. For multiple COVID-19 vaccines, breakthrough infections and COVID-19-related AEs had unexpectedly high normalized frequencies. The normalized frequency for AE death was elevated for multiple vaccines, including COVID-19 vaccines; the associated risk appears to be additive for coadministered combinations of the COVID-19 Janssen vaccine with either the COVID-19 Pfizer-BioNTech BNT162b2 or the COVID-19 Moderna mRNA-1273 vaccine. Multiple manufacturing lots for the COVID-19 Janssen, COVID-19 Pfizer-BioNTech BNT162b2, and Moderna mRNA-1273 vaccines have high AE death normalized frequencies. These observations, combined with rapid AE death onset following vaccination, likely point to possible manufacturing contamination of specific manufacturing lots; endotoxins are a possible causative constituent. The sensitivity to these causative constituent(s) increases with age in the elderly.

ABSTRACT Protollin, a nasal adjuvant, was evaluated in a randomized double-blind phase 1 study of 16 early Alzheimer’s disease (AD) patients to determine safety and to assess its immunomodulatory effects. In a double-blind dose escalation study, subjects received nasal Protollin at doses of 0.1mg, 0.5mg, 1.0mg, and 1.5mg or placebo twice over a two-week period. Treatment was well-tolerated with minimal side effects. Transcriptomic and single-cell analyses demonstrated that prior to treatment, AD blood monocytes had downregulation of phagocytosis-related genes and an increased pro-inflammatory signature. These AD monocyte abnormalities were reversed by nasal Protollin beginning at a dose of 1.0mg. Protollin induced a robust phagocytic gene signature, including upregulation of CD36 , ITGAL , LYST , and FCGR1A . A similar phagocytic signature was observed in brain- infiltrating amyloid-clearing monocytes in an APP Tg mouse model treated with nasal Protollin. Protollin treatment decreased the expression of costimulatory molecules on monocytes and decreased CD8+ T cell activation and cytotoxicity. Our results provide the basis for a phase 2 study of nasal Protollin in subjects with AD in which nasal Protollin at a dose of 1.0 mg will be administered weekly over 6 months to modulate peripheral immunity and clear amyloid from the brain. ClinicalTrials.gov registration no NCT07187141 .

Abstract Background Claudin 18.2 (CLDN18.2) is a validated target in GEC, but novel approaches are needed. Givastomig/ABL111 (giva) is a first-in-class, bispecific antibody targeting tumoral CLDN18.2 and 4-1BB on adjacent T cells, preferentially activating T cells in the tumor microenvironment. Previously, the monotherapy phase 1 data showed that giva was safe and well tolerated in heavily pretreated GEC patients (pts). Here we report updated safety, efficacy, and biomarker data in GEC. Methods The study included dose escalation and dose expansion cohorts. During escalation, pts with solid tumors irrespective of CLDN18.2 expression received giva intravenously every 2 weeks (Q2W) across 8 dose levels (0.1-15 mg/kg), and every three weeks (Q3W) at 18 mg/kg. During expansion, CLDN18.2-positive (CLDN18.2+, ≥1% of tumor cells with ≥1+ intensity by immunohistochemistry) GEC pts were included. Differences in objective response rate (ORR) and disease control rate (DCR) between CLDN18.2-high pts (≥ 75% tumor cells of IHC 2+/3+) and CLDN18.2-low pts were evaluated by Chi-square test. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier method and Cox proportional hazards. Outcomes for CLDN18.2+ GEC pts at doses ≥ 5 mg/kg are reported here. Results As of June 10, 2025, 45 pts with GEC received giva at 5 mg/kg (n=7), 8 mg/kg (n=5), 12 mg/kg (n=21), and 15 mg/kg (n=6) Q2W and 18 mg/kg Q3W (n=6). Pts had received a median of 3 prior therapies, including 74% with prior programmed death-(ligand) 1 inhibitor. No new safety signal was identified with longer follow up. No dose limiting toxicities were observed. Common treatment-related adverse events (≥15%, any grade/grade 3) included anemia (27%/9%), white blood cell count decrease (22%/7%), nausea (20%/2%), and ALT increase (16%/2%), AST increase (16%/4%). Partial responses (PR) were observed in 8 pts (1 PR each at 5 and 8 mg/kg, 4 PRs at 12 mg/kg, and 2 PRs at 18 mg/kg) with an ORR of 18%. CLDN18.2 expression in responders ranged from 11% (1+, 10%; 2+, 1%) to 100% (2+, 10%; 3+, 90%). Stable disease was observed in 14 pts (DCR 49%). 2 (4%) pts are ongoing, with 1 PR at 8 mg/kg at 33 months (mo) and 1 PR at 18 mg/kg at 10 mo. The median PFS (mPFS) and median OS (mOS) are 2.96 mo (95% CI 1.71-3.91) and 7.49 mo (95% CI 4.96-12.5), respectively. There is no statistical difference in ORR, DCR, PFS, or OS between CLDN18.2-high pts (n=21) and CLDN18.2-low pts (n=24): ORR 19% vs. 17% (p=1.00), DCR 57% vs. 42% (p=0.46), mPFS 3.68 mo vs. 1.84 mo, PFS hazard ratio (HR) 0.87 (p=0.67), and mOS 7.49 mo vs. 7.49 mo, OS HR 0.88 (p=0.74), respectively. Conclusions Giva was well tolerated up to 15 mg/kg Q2W and 18 mg/kg Q3W and continues to show encouraging monotherapy activity in heavily pre-treated GEC pts with a wide range of CLDN18.2 expression. Giva may have the ability to target pts with lower CLDN18.2 expression compared with other CLDN18.2 agents and is currently being tested in 1L GEC in combination with immunochemotherapy (NCT04900818). Citation Format: Samuel J. Klempner, Lin Shen, Farshid Dayyani, Jeremy Kratz, Xinjun Liang, Funan Liu, Zenning Wang, Laura Feller, Eugenia Girda, Hongming Pan, Sunnie Kim, Yanhong Deng, Ting Deng, Tianshu Liu, John Powderly, Kristen Spencer, Reva Schneider, Jordan Berlin, Claire (Cong) M. Xu, Christoph M. Ahlers, Xuejun M. Liu, Peter Sabbatini, Jinyoung Park, Yangmi Lim, Juyeun Jeon, Yuan Meng, Geoffrey Ku. Updated Safety, Efficacy and Biomarker Analysis from the Phase I Study of Givastomig, a Novel Claudin 18.2/4-1BB Bispecific Antibody, in Claudin 18.2 Positive Advanced Gastroesophageal Carcinoma (GEC) [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr B016.

Cancer remains a significant global health challenge, with varying incidence and mortality rates across the globe. According to the Surveillance, Epidemiology, and End Results (SEER) registry [1] and the American Cancer Society (ACS) [2], more than 2 million new cancer cases are expected in the US by 2025. Understanding the burden of disease and advancements in tailored treatments, also known as precision or personalized medicine, is crucial for improving patient outcomes. Pharmacogenomics is the study of how an individual’s genetic makeup influences their response to treatment [3]. This field aims to identify genetic variations among individuals (pharmacogenomic variants) to predict drug efficacy and the risk of adverse drug reactions, thereby optimizing and personalizing treatment while minimizing side effects for patients [4]. In the last decade, attention has increasingly shifted beyond the traditional coding genome to noncoding RNAs (ncRNAs), which serve as key regulators of gene expression and biomarkers in cancer, adding complexity to tumor signaling networks.

Phytoremediation has emerged as a sustainable and cost-effective strategy for mitigating contamination in soil and water systems, utilizing plants and their associated microbial consortia to uptake, degrade, or immobilize pollutants. This review synthesizes findings from over 100 peer-reviewed publications and case studies to identify key parameters influencing phytoremediation efficiency, including contaminant bioavailability, chemical speciation, concentration levels (ranging from trace to >100 mg/L), plant species suitability, hydraulic retention time, and temperature ranges (10–35 °C). Despite its proven potential, the absence of standardized design frameworks limits consistent implementation and cross-site performance comparability. To address this, the study proposes a conceptual system design framework supported by measurable performance metrics—such as pollutant removal efficiency (often >70% for heavy metals) and biomass uptake capacity. The review further examines regulatory and policy gaps that hinder the technology’s integration into national remediation strategies, particularly in low- and middle-income countries. It underscores the need for technical guidelines, regulatory benchmarks, and protocols for post-treatment biomass management to enable safe, effective, and scalable deployment. By advocating a multi-stakeholder, evidence-based approach, the study aims to bridge the gap between scientific innovation and environmental governance, positioning phytoremediation as a viable tool for pollution control, ecosystem restoration, and alignment with global sustainability targets.

Food safety relies on rapid detection methods and rigorous sampling of the food processing environment and is challenged by recurrent biofilm contamination and by sublethally injured bacteria that can evade detection. Bactiscan is investigated as an alternative detection approach, a macro-scale and reagentless device that detects microbial contamination through activating the green fluorescence of glycoproteins in the bacterial cell wall. The detection capability of Bactiscan was tested on foodborne pathogens Escherichia coli, Listeria monocytogenes, Salmonella enterica, and Staphylococcus aureus. Detection by Bactiscan was assessed using 3 independent observers viewing bacterial samples dried on stainless steel, using 3 biological repeats and 5 technical repeats. Detection by Bactiscan was possible to 1.20*106 colony forming units (CFU), compared to 1.36*104 CFU by ATP swab testing, where Bactiscan detection limits were defined by the concentration at which 50% of the samples were observed under illumination of the device. Heat-killed and chlorine-stressed E. coli and S. enterica caused a 2-log reduction in detection by ATP swab tests (p≤0.05), while detection by Bactiscan was unaffected (p≥0.05). Pathogen biofilms were detectable via Bactiscan with >80% accuracy at 4days of growth; E. coli and L. monocytogenes biofilms were visible at 2days of growth. In situ contamination studies determined that Bactiscan can detect microbial contamination on chicken, salmon, and yoghurt samples with stronger fluorescence than a competitor's UV torch. The presence of one of the pathogens on the food samples was confirmed by metagenome sequencing, determining that S. aureus was present in 7 samples out of 9 with a relative abundance of >0.5%. These data demonstrate that Bactiscan can effectively detect bacteria present in the food processing environment and can complement existing technologies to improve food industry cleaning practices and infection prevention.

Rheumatoid arthritis (RA) is an immune-mediated, chronic inflammatory condition. With modern therapeutics and evidence-based management strategies, achieving sustained remission is increasingly common. To prevent complications associated with prolonged use of immunosuppressants, drug tapering or withdrawal is recommended. However, due to the lack of tools that define immunological remission, disease flares are frequent, highlighting the need for a more precision medicine-based approach. Utilizing high-dimensional phenotyping platforms, we set out to define peripheral blood immunological signatures of sustained remission in RA. We identified that CD8+CD57+KIR2DL1+ NK cells are associated with sustained remission. Functional studies uncovered an NK cell subset characterized by normal degranulation responses and reduced proinflammatory cytokine expression, which was elevated in sustained remission. Furthermore, flow cytometric analysis of NK cells from synovial fluid combined with interrogation of a publicly available single-cell RNA-Seq dataset of synovial tissue from active RA identified a deficiency of the phenotypic characteristics associated with this NK cell remission signature. In summary, we have uncovered an immune signature of RA remission associated with compositional changes in NK cell phenotype and function that has implications for understanding the effect of sustained remission on host immunity and distinct features that may define operational tolerance in RA.