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Supportive Care in Cancer : Official... Apr 2024Immune-related thyroid adverse events (irTAEs) occur frequently following immune checkpoint inhibitor (ICI) therapy. The purpose of this study is to provide knowledge...
Frequency and characteristics of immune-related thyroid adverse events in patients with resected stage III/IV melanoma treated with adjuvant PD-1 inhibitors: a national cohort study.
PURPOSE
Immune-related thyroid adverse events (irTAEs) occur frequently following immune checkpoint inhibitor (ICI) therapy. The purpose of this study is to provide knowledge about the incidence, clinical timeline characteristics, associated factors of irTAEs, and potential impact on treatment efficacy in patients with melanoma receiving adjuvant ICI therapy.
METHODS
A national multicenter retrospective cohort study of patients with resected stage III/IV melanoma treated with adjuvant PD-1 inhibitors between November 2018 and December 2020. Data were extracted from the Danish Metastatic Melanoma Database. The irTAEs were defined as two consecutive abnormal TSH values and subdivided into transient or persistent.
RESULTS
Of 454 patients, 99 developed an irTAE (21.8%), of these were 46 transient (46.5%) and 53 persistent (53.5%). Median time to transient and persistent irTAE was 55 and 44 days, respectively (p = 0.57). A hyperthyroid phase followed by hypothyroidism was seen in 73.6% of persistent irTAEs, whereas 87% of transient irTAEs developed an isolated hypo- or hyperthyroid phase. Multiple variable analysis demonstrated an association between irTAE and female sex (HR 2.45; 95% CI 1.63-3.70; p < 0.001), but no association with recurrence-free survival (HR 0.86; 95% CI 0.50-1.48; p = 0.587) or overall survival (HR 1.05; 95% CI 0.52-2.12, p = 0.891).
CONCLUSIONS
IrTAE is a common side effect to PD-1 inhibitors primarily occurring within the first 3 months, with a high risk of persistency. Female sex is a strong predictive factor. IrTAE was not associated with improved clinical outcome.
Topics: Humans; Female; Melanoma; Immune Checkpoint Inhibitors; Cohort Studies; Retrospective Studies; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Skin Neoplasms; Hyperthyroidism
PubMed: 38598052
DOI: 10.1007/s00520-024-08445-y -
Journal of Materials Chemistry. B May 2024Vaccines represent one of the most significant inventions in human history and have revolutionized global health. Generally, a vaccine functions by triggering the innate... (Review)
Review
Vaccines represent one of the most significant inventions in human history and have revolutionized global health. Generally, a vaccine functions by triggering the innate immune response and stimulating antigen-presenting cells, leading to a defensive adaptive immune response against a specific pathogen's antigen. As a key element, adjuvants are chemical materials often employed as additives to increase a vaccine's efficacy and immunogenicity. For over 90 years, adjuvants have been essential components in many human vaccines, improving their efficacy by enhancing, modulating, and prolonging the immune response. Here, we provide a timely and comprehensive review of the historical development and the current status of adjuvants, covering their classification, mechanisms of action, and roles in different vaccines. Additionally, we perform systematic analysis of the current licensing processes and highlights notable examples from clinical trials involving vaccine adjuvants. Looking ahead, we anticipate future trends in the field, including the development of new adjuvant formulations, the creation of innovative adjuvants, and their integration into the broader scope of systems vaccinology and vaccine delivery. The article posits that a deeper understanding of biochemistry, materials science, and vaccine immunology is crucial for advancing vaccine technology. Such advancements are expected to lead to the future development of more effective vaccines, capable of combating emerging infectious diseases and enhancing public health.
Topics: Humans; Adjuvants, Vaccine; Vaccines; Animals; Adjuvants, Immunologic
PubMed: 38591323
DOI: 10.1039/d3tb02861e -
Breast Cancer Research : BCR Apr 2024Patients with hormone receptor positive breast cancer are recommended at least five years of adjuvant endocrine therapy, but adherence to this treatment is often...
INTRODUCTION
Patients with hormone receptor positive breast cancer are recommended at least five years of adjuvant endocrine therapy, but adherence to this treatment is often suboptimal. We investigated longitudinal trends in adjuvant endocrine therapy (AET) adherence among premenopausal breast cancer patients and identified clinical characteristics, including baseline comorbidities and non-cancer chronic medication use, associated with AET adherence.
METHODS
We included stage I-III premenopausal breast cancer patients diagnosed during 2002-2011 and registered in the Danish Breast Cancer Group clinical database who initiated AET. We used group-based trajectory modeling to describe AET adherence patterns. We also linked patients to Danish population-based registries and fit multinomial logistic models to compute odds ratios (ORs) and 95% confidence intervals (95% CIs) associating clinical characteristics with AET adherence patterns.
RESULTS
We identified three adherence patterns among 4,353 women-high adherers (57%), slow decliners (36%), and rapid decliners (6.9%). Women with stage I disease (vs. stage II; OR: 1.9, 95% CI 1.5, 2.5), without chemotherapy (vs. chemotherapy; OR: 4.3, 95% CI 3.0, 6.1), with prevalent comorbid disease (Charlson Comorbidity Index score ≥ 1 vs. 0; OR: 1.6, 95% CI 1.1, 2.3), and with a history of chronic non-cancer medication use (vs. none; OR: 1.3, 95% CI 1.0, 1.8) were more likely to be rapid decliners compared with high adherers.
CONCLUSIONS
Women with stage I cancer, no chemotherapy, higher comorbidity burden, and history of chronic non-cancer medication use were less likely to adhere to AET. Taking steps to promote adherence in these groups of women may reduce their risk of recurrence.
Topics: Humans; Female; Breast Neoplasms; Chemotherapy, Adjuvant; Antineoplastic Agents, Hormonal; Medication Adherence; Retrospective Studies
PubMed: 38589932
DOI: 10.1186/s13058-024-01819-4 -
Scientific Reports Apr 2024The aim of the present study was to prepare and evaluate Piperine (PP) loaded chitosan lipid nanoparticles (PP-CLNPs) to evaluate its biological activity alone or in...
The aim of the present study was to prepare and evaluate Piperine (PP) loaded chitosan lipid nanoparticles (PP-CLNPs) to evaluate its biological activity alone or in combination with the antidiabetic drug Metformin (MET) in the management of cognitive deficit in diabetic rats. Piperine was successfully loaded on CLNPs prepared using chitosan, stearic acid, Tween 80 and Tripolyphosphate (TPP) at different concentrations. The developed CLNPs exhibited high entrapment efficiency that ranged from 85.12 to 97.41%, a particle size in the range of 59.56-414 nm and a negatively charged zeta potential values (- 20.1 to - 43.9 mV). In vitro release study revealed enhanced PP release from CLNPs compared to that from free PP suspensions for up to 24 h. In vivo studies revealed that treatment with the optimized PP-CLNPs formulation (F2) exerted a cognitive enhancing effect and ameliorated the oxidative stress associated with diabetes. PP-CLNPs acted as an effective bio-enhancer which increased the potency of metformin in protecting brain tissue from diabetes-induced neuroinflammation and memory deterioration. These results suggested that CLNPs could be a promising drug delivery system for encapsulating PP and thus can be used as an adjuvant therapy in the management of high-risk diabetic cognitive impairment conditions.
Topics: Rats; Animals; Rats, Wistar; Chitosan; Diabetes Mellitus, Experimental; Nanoparticles; Cognitive Dysfunction; Cognition; Metformin; Particle Size; Drug Carriers; Polyunsaturated Alkamides; Liposomes; Piperidines; Benzodioxoles; Alkaloids
PubMed: 38589438
DOI: 10.1038/s41598-024-58601-x -
PharmacoEconomics - Open May 2024This study aims to estimate the budget impact of luspatercept reimbursement as an adjuvant to the standard management of β-thalassaemia major in Cyprus, from a societal...
OBJECTIVE
This study aims to estimate the budget impact of luspatercept reimbursement as an adjuvant to the standard management of β-thalassaemia major in Cyprus, from a societal perspective, and assess the financial feasibility of its inclusion in the β-thalassaemia armamentarium.
METHODS
A 5-year horizon budget impact model was developed to determine the budget impact of reimbursing luspatercept for the management of β-thalassaemia major in Cyprus. Two treatment discontinuation scenarios were elaborated. In the first scenario, luspatercept is reimbursed complementary to best supportive care, and a dropout rate of 40% is assumed based on published real-world data, while for the second scenario a dropout rate of 25%, is assumed as per the clinical trial data. Input parameters were retrieved from the phase III clinical trial of luspatercept, literature, and expert opinion consensus. One-way sensitivity analyses were conducted for both scenarios.
RESULTS
The addition of luspatercept to the standard management of β-thalassaemia major in Cyprus imparted an incremental budget impact ranging from €21,300,643 to €25,834,368, depending on the drop-out rate scenario assumed. Results were sensitive to the number of eligible patients and dose per patient.
CONCLUSION
The potential reimbursement of luspatercept will wield a substantial impact on Cyprus total pharmaceutical expenditure and it is therefore imperative to affix a reimbursement framework that will allow the payer to mitigate uncertainty stemming out of the scarce clinical data and the inherently complex therapeutic landscape of β-thalassemia management.
PubMed: 38575797
DOI: 10.1007/s41669-024-00482-x -
PloS One 2024Selection of adjuvant to be combined with the antigen is an extremely important point for formulating effective vaccines. The aim of this study was to evaluate...
Selection of adjuvant to be combined with the antigen is an extremely important point for formulating effective vaccines. The aim of this study was to evaluate reactogenicity, levels of IgM, IgG and subclasses (IgG1, IgG2b and IgG3), and protection elicited by vaccine formulations with association of chitosan coated alginate or Montanide ISA 61 with γ-irradiated Brucella ovis. The alginate/chitosan biopolymers as well as the Montanide ISA 61 emulsion elicited intense and long-lasting local response, especially when associated with the antigen. However, Montanide ISA 61 induced less intense reactogenicity when compared to alginate/chitosan. Furthermore, γ-irradiated B. ovis with Montanide ISA 61 induced higher levels of IgG2b an important marker of cellular immune response. In conclusion, Montanide ISA 61 resulted in milder reactogenicity when compared to the alginate/chitosan, while it induced a high IgG2b/IgG1 ratio compatible with a Th1 profile response.
Topics: Animals; Mice; Sheep; Adjuvants, Vaccine; Chitosan; Capsules; Adjuvants, Immunologic; Vaccines; Immunoglobulin G; Mice, Inbred BALB C; Mineral Oil
PubMed: 38573916
DOI: 10.1371/journal.pone.0298117 -
STAR Protocols Jun 2024Mincle (macrophage-inducible C-type lectin, CLEC4E) is a C-type lectin immune-stimulatory receptor that can be targeted for inducing potent adjuvant effects. Mincle can...
Mincle (macrophage-inducible C-type lectin, CLEC4E) is a C-type lectin immune-stimulatory receptor that can be targeted for inducing potent adjuvant effects. Mincle can recognize trehalose dimycolate and related glycolipids. Here, we present a protocol to identify the ligand binding mode of Mincle. We describe steps for preparing labeled Mincle ectodomain, data acquisition, and analysis of nuclear magnetic resonance experiments using non-detergent sulfobetaine-195. This protocol can be applied to other protein-ligand interactions that have aggregation problems for complex formation. For complete details on the use and execution of this protocol, please refer to Furukawa et al..
Topics: Lectins, C-Type; Ligands; Binding Sites; Humans; Magnetic Resonance Spectroscopy; Protein Binding; Receptors, Immunologic; Membrane Proteins; Nuclear Magnetic Resonance, Biomolecular
PubMed: 38573861
DOI: 10.1016/j.xpro.2024.102996 -
ACS Nano Apr 2024The cGAS-STING pathway plays a crucial role in innate immune activation against cancer and infections, and STING agonists based on cyclic dinucleotides (CDN) have...
The cGAS-STING pathway plays a crucial role in innate immune activation against cancer and infections, and STING agonists based on cyclic dinucleotides (CDN) have garnered attention for their potential use in cancer immunotherapy and vaccines. However, the limited drug-like properties of CDN necessitate an efficient delivery system to the immune system. To address these challenges, we developed an immunostimulatory delivery system for STING agonists. Here, we have examined aqueous coordination interactions between CDN and metal ions and report that CDN mixed with Zn and Mn formed distinctive crystal structures. Further pharmaceutical engineering led to the development of a functional coordination nanoparticle, termed the Zinc-Mn-CDN Particle (ZMCP), produced by a simple aqueous one-pot synthesis. Local or systemic administration of ZMCP exerted robust antitumor efficacy in mice. Importantly, recombinant protein antigens from SARS-CoV-2 can be simply loaded during the aqueous one-pot synthesis. The resulting ZMCP antigens elicited strong cellular and humoral immune responses that neutralized SARS-CoV-2, highlighting ZMCP as a self-adjuvant vaccine platform against COVID-19 and other infectious pathogens. Overall, this work establishes a paradigm for developing translational coordination nanomedicine based on drug-metal ion coordination and broadens the applicability of coordination medicine for the delivery of proteins and other biologics.
Topics: Animals; Mice; Neoplasms; Adjuvants, Immunologic; Immunotherapy; Vaccines; Nanoparticles
PubMed: 38567994
DOI: 10.1021/acsnano.3c11374 -
Chinese Medicine Apr 2024Acute promyelocytic leukemia (APL), which was once considered one of the deadliest types of leukemia, has become a curable malignancy since the introduction of all-trans... (Review)
Review
Acute promyelocytic leukemia (APL), which was once considered one of the deadliest types of leukemia, has become a curable malignancy since the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) as clinical treatments. ATO, which has become the first-line therapeutic agent for APL, is derived from the natural mineral product arsenic, exemplifying an important role of natural products in the treatment of APL. Many other natural products, ranging from small-molecule compounds to herbal extracts, have also demonstrated great potential for the treatment and adjuvant therapy of APL. In this review, we summarize the natural products and representative components that have demonstrated biological activity for the treatment of APL. We also discuss future directions in better exploring their medicinal value, which may provide a reference for subsequent new drug development and combination therapy programs.
PubMed: 38566147
DOI: 10.1186/s13020-024-00928-8 -
Oncology Research and Treatment 2024S-1 has been shown to be an effective adjuvant treatment option for East Asian patients who underwent gastrectomy for stage II/III gastric cancer. We conducted a phase...
Adjuvant Treatment with S-1 in Patients after R0-Resection of Adenocarcinoma of the Stomach and Esophagogastric Junction: A Multicenter Phase I/II Feasibility Study (GMBH-STO-0114).
INTRODUCTION
S-1 has been shown to be an effective adjuvant treatment option for East Asian patients who underwent gastrectomy for stage II/III gastric cancer. We conducted a phase I/II study to evaluate the feasibility, tolerability, and efficacy of administering S-1 in the adjuvant setting after R0-resection of adenocarcinoma of the stomach and esophagogastric junction (EGJ) in Caucasian patients.
METHODS
In this single-cohort, open-label, phase I/II trial, we enrolled patients with locally advanced adenocarcinoma of the stomach or EGJ having undergone R0-resection with or without neoadjuvant treatment. One treatment cycle consisted of oral S-1 (30 mg/m2 bid) for 14 days. Cycles were repeated every 3 weeks for 18 cycles (54 weeks). Primary endpoint was feasibility and tolerability. Safety was evaluated according to the Common Toxicity Criteria Adverse Events (CTCAE) version 4.0. Secondary endpoints were 1-year relapse-free survival (RFS) rate, RFS, and overall survival (OS).
RESULTS
Between October 2015 and February 2018, 32 patients were enrolled in 12 German centers, and 30 started adjuvant study treatment. Seventeen patients completed all 18 cycles. Two patients terminated study treatment early due to adverse events (AEs), 7 due to patient's or investigator's decision, and 4 due to recurrence or distant metastasis during adjuvant therapy. Dose levels were reduced to 25 mg/m2 in 9 patients and to 20 mg/m2 in 1 patient. Of patients completing all 18 cycles, 5 did so with reduced dosage of S-1. Documented grade ≥3 AEs were neutropenia, diarrhea, vomiting, polyneuropathy, palmar-plantar erythrodysaesthesia, and rash. Serious AEs were observed in 7 patients. Median RFS was 32.2 months. One-year RFS rate was 77%. Data on OS were still premature at the end of the study.
CONCLUSION
Adjuvant treatment with S-1 for 1 year is a feasible and safe treatment option for Caucasian patients diagnosed with gastric adenocarcinoma or cancer of the EGJ after R0-resection.
Topics: Humans; Stomach Neoplasms; Tegafur; Male; Oxonic Acid; Drug Combinations; Middle Aged; Female; Esophagogastric Junction; Adenocarcinoma; Feasibility Studies; Aged; Chemotherapy, Adjuvant; Gastrectomy; Adult; Treatment Outcome; Antimetabolites, Antineoplastic; Esophageal Neoplasms
PubMed: 38565089
DOI: 10.1159/000538143