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NEJM Evidence Nov 2022The long-term outcome of patients with stage III melanoma - that is, melanoma that has spread to nearby lymph nodes, lymphatics, or skin - who have received treatment...
The long-term outcome of patients with stage III melanoma - that is, melanoma that has spread to nearby lymph nodes, lymphatics, or skin - who have received treatment with immune checkpoint inhibitors is of substantial interest. The article by Eggermont et al. published in this issue of reports 5-year outcomes from the stage III melanoma trial, KEYNOTE-054, which compared pembrolizumab (anti-programmed cell death protein 1 [PD-1]) with placebo. The data show durable recurrence-free survival (RFS) and distant metastasis-free survival (DMFS).
Topics: Humans; Melanoma; Skin Neoplasms; Progression-Free Survival; Adjuvants, Immunologic; Adjuvants, Pharmaceutic
PubMed: 38319859
DOI: 10.1056/EVIDe2200240 -
Biomedicine & Pharmacotherapy =... Sep 2018Research over the past several decades has provided insight into the mode of action of adjuvants. However, the main focus of attention has been the efficacy in the... (Review)
Review
Research over the past several decades has provided insight into the mode of action of adjuvants. However, the main focus of attention has been the efficacy in the induction of protective immunogenicity, while less effort has been devoted to the study of toxicity mechanisms. Evidences suggest that several mechanisms that are responsible for the immunostimulating effects are, at the same time, responsible of the adverse effects. In this context, it is often very difficult to establish the boundaries between immunostimulation and immunotoxicity to reach the ideal balance of efficacy/safety. During decades, hundreds of adjuvants and adjuvant formulations have been proposed as immunostimulants for vaccines but very few have been used in human vaccines due to toxicity concerns. In this review, relevant aspects about immunotoxicology of adjuvants, based on clinical and experimental studies are discussed. Some effects are only observed under hyperstimulating regimens using non-approved adjuvants for human use, but these are nonetheless useful to understanding basic principles of adjuvant toxicity. The acute local and systemic reactions, during the first hours and those that can be observed after the third day of vaccination in the inoculation site and systemically are discussed.
Topics: Adaptive Immunity; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Animals; Drug-Related Side Effects and Adverse Reactions; Humans; Immunity, Innate; Vaccines
PubMed: 29894962
DOI: 10.1016/j.biopha.2018.06.026 -
PloS One 2023Considering the pharmacological treatment options for endometriosis-associated pain are confined to hormonal therapy and analgesics, we studied the analgesic effect of... (Randomized Controlled Trial)
Randomized Controlled Trial
Considering the pharmacological treatment options for endometriosis-associated pain are confined to hormonal therapy and analgesics, we studied the analgesic effect of 20 mg melatonin as an adjuvant therapy in women with endometriosis-associated pain. This randomized double-blinded, placebo-controlled trial was conducted at the Research Center for Womens' Health at Södersjukhuset, a university hospital in Stockholm, Sweden. Forty women from 18 to 50 years of age with endometriosis and severe dysmenorrhea with or without chronic pelvic pain were given 20 mg Melatonin or placebo orally daily for two consecutive menstrual cycles or months. The level of pain was recorded daily on the 11-point numeric rating scale, a difference of 1.3 units was considered clinically significant. Clincaltrials.gov nr NCT03782740. Sixteen participants completed the study in the placebo group and 18 in the melatonin group. The difference in endometriosis-associated pain between the groups showed to be non-significant statistically as well as clinically, 2.9 (SD 1.9) in the melatonin group and 3.3 (SD 2.0) in the placebo group, p = 0.45. This randomized, double-blinded, placebo-controlled trial could not show that 20 mg of melatonin given orally at bedtime had better analgesic effect on endometriosis-associated pain compared with placebo. No adverse effects were observed.
Topics: Female; Humans; Infant; Endometriosis; Melatonin; Pain Management; Pelvic Pain; Analgesics; Adjuvants, Pharmaceutic; Double-Blind Method; Dysmenorrhea; Treatment Outcome
PubMed: 37267394
DOI: 10.1371/journal.pone.0286182 -
Scientific Reports Sep 2023Ewing sarcoma (EWS) is a malignant tumor arising in bone or soft tissue that occurs in adolescent and young adult patients as well as adults later in life. Although...
Ewing sarcoma (EWS) is a malignant tumor arising in bone or soft tissue that occurs in adolescent and young adult patients as well as adults later in life. Although non-metastatic EWS is typically responsive to treatment when newly diagnosed, relapsed cases have an unmet need for which no standard treatment approach exists. Recent phase III clinical trials for EWS comparing 7 vs 5 chemotherapy drugs have failed to improve survival. To extend the durability of remission for EWS, we investigated 3 non-chemotherapy adjuvant therapy drug candidates to be combined with chemotherapy. The efficacy of these adjuvant drugs was investigated via anchorage-dependent growth assays, anchorage-independent soft-agar colony formation assays and EWS xenograft mouse models. Enoxacin and entinostat were the most effective adjuvant drug in both long-term in vitro and in vivo adjuvant studies. In the context that enoxacin is an FDA-approved antibiotic, and that entinostat is an investigational agent not yet FDA-approved, we propose enoxacin as an adjuvant drug for further preclinical and clinical investigation in EWS patients.
Topics: Humans; Animals; Mice; Sarcoma, Ewing; Enoxacin; Neuroectodermal Tumors, Primitive, Peripheral; Benzamides; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Disease Models, Animal; Tumor Suppressor Protein p53
PubMed: 37658148
DOI: 10.1038/s41598-023-40751-z -
Biomaterials Science Jul 2022Vaccination is a proven way to protect individuals against many infectious diseases, as currently highlighted in the global COVID-19 pandemic. Peptides- or small... (Review)
Review
Vaccination is a proven way to protect individuals against many infectious diseases, as currently highlighted in the global COVID-19 pandemic. Peptides- or small molecule antigen-based vaccination offer advantages over the classical vaccine approaches. However, peptides or small molecules by themselves are generally not sufficiently immunogenic, and thus require an adjuvant to boost an immune response. Several conjugated systems have been developed in recent years to overcome this obstacle. This review summarises different moieties which, when conjugated to peptide antigens, facilitate a specific immune response. Different classes of self-adjuvant moieties are reviewed, including self-assembly peptides, lipids, glycolipids, and polymers.
Topics: Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Antigens; COVID-19; Humans; Pandemics; Peptides; Vaccine Development
PubMed: 35708540
DOI: 10.1039/d2bm00061j -
Scientific Reports Sep 2023Upregulation of neuroplasticity might help maximize stroke recovery. One intervention that appears worthy of investigation is aerobic exercise. This study aimed to... (Randomized Controlled Trial)
Randomized Controlled Trial
Upregulation of neuroplasticity might help maximize stroke recovery. One intervention that appears worthy of investigation is aerobic exercise. This study aimed to determine whether a single bout of moderate intensity aerobic exercise can enhance neuroplasticity in people with stroke. Participants were randomly assigned (1:1) to a 20-min moderate intensity exercise intervention or remained sedentary (control). Transcranial magnetic stimulation measured corticospinal excitability of the contralesional hemisphere by recording motor evoked potentials (MEPs). Intermittent Theta Burst Stimulation (iTBS) was used to repetitively activate synapses in the contralesional primary motor cortex, initiating the early stages of neuroplasticity and increasing excitability. It was surmised that if exercise increased neuroplasticity, there would be a greater facilitation of MEPs following iTBS. Thirty-three people with stroke participated in this study (aged 63.87 ± 10.30 years, 20 male, 6.13 ± 4.33 years since stroke). There was an interaction between Time*Group on MEP amplitudes (P = 0.009). Participants allocated to aerobic exercise had a stronger increase in MEP amplitude following iTBS. A non-significant trend indicated time since stroke might moderate this interaction (P = 0.055). Exploratory analysis suggested participants who were 2-7.5 years post stroke had a strong MEP facilitation following iTBS (P < 0.001). There was no effect of age, sex, resting motor threshold, self-reported physical activity levels, lesion volume or weighted lesion load (all P > 0.208). Moderate intensity cycling may enhance neuroplasticity in people with stroke. This therapy adjuvant could provide opportunities to maximize stroke recovery.
Topics: Humans; Male; Animals; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Bicycling; Exercise; Gastropoda; Neuronal Plasticity; Stroke
PubMed: 37660093
DOI: 10.1038/s41598-023-40902-2 -
Journal of the American Geriatrics... Apr 2020The adjuvant analgesics are a large and diverse group of drugs that were developed for primary indications other than pain and are potentially useful analgesics for one... (Review)
Review
The adjuvant analgesics are a large and diverse group of drugs that were developed for primary indications other than pain and are potentially useful analgesics for one or more painful conditions. The "adjuvant" designation reflects their early use as opioid co-analgesics for cancer pain. During the past 3 decades, their role in pain management has changed with the advent of many new entities, emerging data from numerous analgesic trials, and growing clinical experience. Many of these drugs are now used as primary analgesics for specific types of chronic pain. With proper patient selection and cautious administration, they can potentially contribute meaningfully to the management of chronic pain in older adults. A practical approach categorizes the many adjuvant analgesics by broad indications: multipurpose drugs and drugs that target neuropathic pain, musculoskeletal pain, and cancer pain, respectively. This article reviews the status of the evidence supporting the analgesic potential of the adjuvant analgesics and discusses best practices in terms of drug selection and dosing. J Am Geriatr Soc 68:691-698, 2020.
Topics: Adjuvants, Pharmaceutic; Aged; Analgesics; Cancer Pain; Chronic Pain; Humans; Musculoskeletal Pain; Neuralgia; Pain Management
PubMed: 32216151
DOI: 10.1111/jgs.16340 -
Theranostics 2023Glioblastoma multiforme (GBM) is the most common and lethal type of adult brain cancer. Current GBM standard of care, including radiotherapy, often ends up with cancer...
Glioblastoma multiforme (GBM) is the most common and lethal type of adult brain cancer. Current GBM standard of care, including radiotherapy, often ends up with cancer recurrence, resulting in limited long-term survival benefits for GBM patients. Immunotherapy, such as immune checkpoint blockade (ICB), has thus far shown limited clinical benefit for GBM patients. Therapeutic vaccines hold great potential to elicit anti-cancer adaptive immunity, which can be synergistically combined with ICB and radiotherapy. Peptide vaccines are attractive for their ease of manufacturing and stability, but their therapeutic efficacy has been limited due to poor vaccine co-delivery and the limited ability of monovalent antigen vaccines to prevent tumor immune evasion. To address these challenges, here, we report GBM radioimmunotherapy that combines radiotherapy, ICB, and multivalent lymph-node-targeting adjuvant/antigen-codelivering albumin-binding vaccines (AAco-AlbiVax). Specifically, to codeliver peptide neoantigens and adjuvant CpG to lymph nodes (LNs), we developed AAco-AlbiVax based on a Y-shaped DNA scaffold that was site-specifically conjugated with CpG, peptide neoantigens, and albumin-binding maleimide-modified Evans blue derivative (MEB). As a result, these vaccines elicited antitumor immunity including neoantigen-specific CD8 T cell responses in mice. In orthotopic GBM mice, the combination of AAco-AlbiVax, ICB, and fractionated radiation enhanced GBM therapeutic efficacy. However, radioimmunotherapy only trended more efficacious over radiotherapy alone. Taken together, these studies underscore the great potential of radioimmunotherapy for GBM, and future optimization of treatment dosing and scheduling would improve the therapeutic efficacy.
Topics: Animals; Mice; Glioblastoma; Radioimmunotherapy; Neoplasm Recurrence, Local; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Vaccines; Albumins; Lymph Nodes
PubMed: 37649594
DOI: 10.7150/thno.84443 -
Current Issues in Molecular Biology 2017Poor immunogenicity remains the single biggest obstacle to human DNA vaccines achieving their potential. Strategies to improve DNA vaccine efficacy include codon... (Review)
Review
Poor immunogenicity remains the single biggest obstacle to human DNA vaccines achieving their potential. Strategies to improve DNA vaccine efficacy include codon optimization, transfection reagents, electroporation, vaccine adjuvants or combination with a protein or vector boost. Increased understanding of molecular events driving innate and adaptive immune responses has assisted development of molecular adjuvants for DNA vaccine use. Such adjuvants comprise plasmid-encoded signalling molecules including cytokines, chemokines, immune costimulatory molecules, toll-like receptor agonists or inhibitors of immune suppressive pathways. New approaches including gene knockdown, epigenetics and systems biology have also contributed to an increased range of molecular adjuvant options. This review explores current and future trends in vaccine design including the latest molecular adjuvants for enhanced DNA vaccine efficacy.
Topics: Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Humans; Vaccines, DNA
PubMed: 27648581
DOI: 10.21775/cimb.022.017 -
International Journal of Molecular... Aug 2023Saponins are a diverse group of naturally occurring plant secondary metabolites present in a wide range of foods ranging from grains, pulses, and green leaves to sea... (Review)
Review
Saponins are a diverse group of naturally occurring plant secondary metabolites present in a wide range of foods ranging from grains, pulses, and green leaves to sea creatures. They consist of a hydrophilic sugar moiety linked to a lipophilic aglycone, resulting in an amphiphilic nature and unique functional properties. Their amphiphilic structures enable saponins to exhibit surface-active properties, resulting in stable foams and complexes with various molecules. In the context of food applications, saponins are utilized as natural emulsifiers, foaming agents, and stabilizers. They contribute to texture and stability in food products and have potential health benefits, including cholesterol-lowering and anticancer effects. Saponins possess additional bioactivities that make them valuable in the pharmaceutical industry as anti-inflammatory, antimicrobial, antiviral, and antiparasitic agents to name a few. Saponins can demonstrate cytotoxic activity against cancer cell lines and can also act as adjuvants, enhancing the immune response to vaccines. Their ability to form stable complexes with drugs further expands their potential in drug delivery systems. However, challenges such as bitterness, cytotoxicity, and instability under certain conditions need to be addressed for effective utilization of saponins in foods and related applications. In this paper, we have reviewed the chemistry, functionality, and application aspects of saponins from various plant sources, and have summarized the regulatory aspects of the food-based application of quillaja saponins. Further research to explore the full potential of saponins in improving food quality and human health has been suggested. It is expected that this article will be a useful resource for researchers in food, feed, pharmaceuticals, and material science.
Topics: Humans; Saponins; Food; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Antiparasitic Agents
PubMed: 37686341
DOI: 10.3390/ijms241713538