-
Nature Reviews. Clinical Oncology Jan 2015Inhibition of poly(ADP-ribose) polymerase (PARP) enzymes is a potential synthetic lethal therapeutic strategy in cancers harbouring specific DNA-repair defects,... (Review)
Review
Inhibition of poly(ADP-ribose) polymerase (PARP) enzymes is a potential synthetic lethal therapeutic strategy in cancers harbouring specific DNA-repair defects, including those arising in carriers of BRCA1 or BRCA2 mutations. Since the development of first-generation PARP inhibitors more than a decade ago, numerous clinical trials have been performed to validate their safety and efficacy, bringing us to the stage at which adjuvant therapy with PARP inhibitors is now being considered as a viable treatment option for patients with breast cancer. Nevertheless, the available data do not provide clear proof that these drugs are efficacious in the setting of metastatic disease. Advancement of a therapy to the neoadjuvant and adjuvant settings without such evidence is exceptional, but seems reasonable in the case of PARP inhibitors because the target population that might benefit from this class of drugs is small and well defined. This Review describes the evolution of PARP inhibitors from bench to bedside, and provides an up-to-date description of the key published or otherwise reported clinical trials of these agents. The specific considerations and challenges that might be encountered when implementing these compounds in the adjuvant treatment of breast cancer in the clinic are also highlighted.
Topics: Adjuvants, Pharmaceutic; Antineoplastic Agents; BRCA1 Protein; BRCA2 Protein; Benzamides; Breast Neoplasms; Carboplatin; DNA Breaks, Double-Stranded; DNA Breaks, Single-Stranded; DNA Repair; Deoxycytidine; Female; Humans; Phthalazines; Piperazines; Poly(ADP-ribose) Polymerase Inhibitors; Gemcitabine
PubMed: 25286972
DOI: 10.1038/nrclinonc.2014.163 -
Expert Review of Anti-infective Therapy 2016The current antibiotic crisis to treat infections by Acinetobacter baumannii is linked with the increase of antimicrobial resistance and the lack of development of new...
The current antibiotic crisis to treat infections by Acinetobacter baumannii is linked with the increase of antimicrobial resistance and the lack of development of new antimicrobial drugs. For this reason, new alternatives for the treatment and control of infections by A. baumannii are necessary. Several studies have reported the effect of adjuvants to restore the efficacy of existing antimicrobial agents. Herein, we analyzed the main results on the development of adjuvant drugs, as monotherapy or in combination therapy with existing antimicrobial agents, which have shown promising results in vitro and in vivo. However, caution is needed and further extensive in vivo studies have to be performed to confirm the potential use of these adjuvants as true therapeutic alternatives.
Topics: Acinetobacter Infections; Acinetobacter baumannii; Adjuvants, Pharmaceutic; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Indoles; Lysophosphatidylcholines; Pyrans; Steroids
PubMed: 26620637
DOI: 10.1586/14787210.2016.1126508 -
Methods in Molecular Biology (Clifton,... 2022The issues of vaccine potency and stability constitute formidable challenges associated with the development and readiness of vaccines for biodefense. In most instances,...
The issues of vaccine potency and stability constitute formidable challenges associated with the development and readiness of vaccines for biodefense. In most instances, the vaccines will be stockpiled (at considerable cost) for years and used only in the rare event of a public health emergency. It is therefore imperative that there be means to readily monitor overall stability of the stockpiled vaccines, preferably using reliable in vitro assays, without the need for expensive and labor-intensive animal studies. In this chapter, we describe an in vitro monoclonal antibody-based competition ELISA known as RiCoE for assessing the potency of a ricin toxin subunit vaccine. RiCoE can be applied to drug substance and drug products adsorbed to aluminum salts adjuvant. While RiCoE is specific for ricin toxin, the general methodologies and protocols described herein are amenable to virtually any subunit or even virus-like particle-based vaccine. Ultimately, RiCoE-like assays may replace or at least reduce the need for animal studies in vaccine potency determinations.
Topics: Adjuvants, Pharmaceutic; Animals; Antibodies, Neutralizing; Ricin; Vaccine Potency; Vaccines, Subunit; Vaccines, Virus-Like Particle
PubMed: 34914076
DOI: 10.1007/978-1-0716-1884-4_37 -
Frontiers in Immunology 2022Adjuvants are important vaccine components, composed of a variety of chemical and biological materials that enhance the vaccine antigen-specific immune responses by...
Adjuvants are important vaccine components, composed of a variety of chemical and biological materials that enhance the vaccine antigen-specific immune responses by stimulating the innate immune cells in both direct and indirect manners to produce a variety cytokines, chemokines, and growth factors. It has been developed by empirical methods for decades and considered difficult to choose a single screening method for an ideal vaccine adjuvant, due to their diverse biochemical characteristics, complex mechanisms of, and species specificity for their adjuvanticity. We therefore established a robust adjuvant screening strategy by combining multiparametric analysis of adjuvanticity and immunological profiles (such as cytokines, chemokines, and growth factor secretion) of various library compounds derived from hot-water extracts of herbal medicines, together with their diverse distribution of nano-sized physical particle properties with a machine learning algorithm. By combining multiparametric analysis with a machine learning algorithm such as rCCA, sparse-PLS, and DIABLO, we identified that human G-CSF and mouse RANTES, produced upon adjuvant stimulation , are the most robust biological parameters that can predict the adjuvanticity of various library compounds. Notably, we revealed a certain nano-sized particle population that functioned as an independent negative parameter to adjuvanticity. Finally, we proved that the two-step strategy pairing the negative and positive parameters significantly improved the efficacy of screening and a screening strategy applying principal component analysis using the identified parameters. These novel parameters we identified for adjuvant screening by machine learning with multiple biological and physical parameters may provide new insights into the future development of effective and safe adjuvants for human use.
Topics: Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Adjuvants, Vaccine; Animals; Cytokines; Herbal Medicine; Machine Learning; Mice; Vaccines
PubMed: 35663999
DOI: 10.3389/fimmu.2022.847616 -
Frontiers in Immunology 2023Vaccine adjuvant research is being fueled and driven by progress in the field of innate immunity that has significantly advanced in the past two decades with the... (Review)
Review
Vaccine adjuvant research is being fueled and driven by progress in the field of innate immunity that has significantly advanced in the past two decades with the discovery of countless innate immune receptors and innate immune pathways. Receptors for pathogen-associated molecules (PAMPs) or host-derived, danger-associated molecules (DAMPs), as well as molecules in the signaling pathways used by such receptors, are a rich source of potential targets for agonists that enable the tuning of innate immune responses in an unprecedented manner. Targeted modulation of immune responses is achieved not only through the choice of immunostimulator - or select combinations of adjuvants - but also through formulation and systematic modifications of the chemical structure of immunostimulatory molecules. The use of medium and high-throughput screening methods for finding immunostimulators has further accelerated the identification of promising novel adjuvants. However, despite the progress that has been made in finding new adjuvants through systematic screening campaigns, the process is far from perfect. A major bottleneck that significantly slows the process of turning confirmed or putative innate immune receptor agonists into vaccine adjuvants continues to be the lack of defined correlates of adjuvanticity. This brief review discusses recent developments, exciting trends, and notable successes in the adjuvant research field, albeit acknowledging challenges and areas for improvement.
Topics: Adjuvants, Immunologic; Immunity, Innate; Adjuvants, Pharmaceutic; Receptors, Immunologic; Signal Transduction
PubMed: 36742311
DOI: 10.3389/fimmu.2023.1105655 -
Methods in Molecular Biology (Clifton,... 2022Spherical or discoidal lipid polymer nanostructures bearing cationic charges successfully adsorb a variety of oppositely charged antigens (Ag) such as proteins,...
Spherical or discoidal lipid polymer nanostructures bearing cationic charges successfully adsorb a variety of oppositely charged antigens (Ag) such as proteins, peptides, nucleic acids, or oligonucleotides. This report provides instructions for the preparation and physical characterization of four different cationic nanostructures able to combine and deliver antigens to the immune system: (1) dioctadecyl dimethylammonium bromide (DODAB) bilayer fragments (DODAB BF); (2) polystyrene sulfate (PSS) nanoparticles (NPs) covered with one cationic dioctadecyl dimethylammonium bromide bilayer (DODAB) named (PSS/DODAB); (3) cationic NPs of biocompatible polymer poly(methyl methacrylate) (PMMA) prepared by emulsion polymerization of the methyl methacrylate (MMA) monomer in the presence of DODAB BF (PMMA/DODAB NPs); (4) antigen NPs (NPs) where the cationic polymer poly(diallyl dimethyl ammonium chloride) (PDDA) directly combined at nontoxic and low dose with the antigen (Ag); when the oppositely charged model antigen is ovalbumin (OVA), NPs are named PDDA/OVA. These nanostructures provide adequate microenvironments for carrying and delivering antigens to the antigen-presenting cells of the immune system.
Topics: Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Cations; Nanoparticles; Ovalbumin; Polymers; Polymethyl Methacrylate; Quaternary Ammonium Compounds; Vaccines
PubMed: 34918247
DOI: 10.1007/978-1-0716-1892-9_10 -
The Journal of Maternal-fetal &... Feb 2018In this review, we discuss the potential use of antimalarial drugs as an adjuvant therapy for preeclampsia, focusing on the mechanisms of action of this class of drugs... (Review)
Review
In this review, we discuss the potential use of antimalarial drugs as an adjuvant therapy for preeclampsia, focusing on the mechanisms of action of this class of drugs in the context of preeclampsia. In particular, hydroxychloroquine has been shown to have various beneficial effects on patients with systemic lupus erythematosus. There are several pathways targeted by the antimalarial drugs that are similar to the pathophysiology of preeclampsia and hence offering opportunities to develop novel therapies to treat the disease. Given the safety profile of hydroxychloroquine in pregnancy, there is merit in exploring the efficacy of this drug as an adjuvant therapy in women with early onset preeclampsia.
Topics: Adjuvants, Pharmaceutic; Antimalarials; Female; Humans; Hydroxychloroquine; Lupus Erythematosus, Systemic; Pre-Eclampsia; Pregnancy
PubMed: 28142291
DOI: 10.1080/14767058.2017.1289511 -
MMW Fortschritte Der Medizin Sep 2019
Review
Topics: Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Herpes Zoster; Herpes Zoster Vaccine; Humans
PubMed: 31494877
DOI: 10.1007/s15006-019-0844-6 -
Medicine Sep 2023Atypical antipsychotic (AAP) augmentation is an alternative strategy for patients with major depressive disorder (MDD) who had an inadequate response to antidepressant... (Meta-Analysis)
Meta-Analysis
Comparative efficacy and safety of 4 atypical antipsychotics augmentation treatment for major depressive disorder in adults: A systematic review and network meta-analysis.
BACKGROUND
Atypical antipsychotic (AAP) augmentation is an alternative strategy for patients with major depressive disorder (MDD) who had an inadequate response to antidepressant therapy (ADT). We aimed to compare and rank the efficacy and safety of 4 AAPs in the adjuvant treatment of MDD.
METHODS
We searched randomized controlled trials (RCTs) published and unpublished from the date of databases and clinical trial websites inception to April 30, 2023. The evidence risk of bias (RoB) and certainty are assessed using the Cochrane bias risk tool and grading of recommendations assessment, development, and evaluation (GRADE) framework, respectively. Using network meta-analysis, we estimated summary risk ratios (RRs) or standardized mean difference (SMD) based on the random effects model.
RESULTS
56 eligible studies comprising 11448 participants were included. In terms of primary efficacy outcome, compared with placebo (PBO), all AAPs had significant efficacy (SMD = -0.40; 95% CI, -0.68 to -0.12 for quetiapine (QTP); -0.35, -0.59 to -0.11 for olanzapine (OLA); -0.28, -0.47 to -0.09 for aripiprazole (ARI) and -0.25, -0.42 to -0.07 for brexpiprazole (BRE), respectively). In terms of acceptability, no significant difference was found, either agents versus agents or agents versus PBO. In terms of tolerability, compared with the PBO, QTP (RR = 0.24; 95% CI,0.11-0.53), OLA (0.30,0.10-0.55), ARI (0.39,0.22-0.69), and BRE (0.37,0.18-0.75) were significantly less well tolerated. 8 (14.2%) of 56 trials were assessed as low RoB, 38 (67.9%) trials had moderate RoB, and 10 (17.9%) had high RoB; By the GRADE, the certainty of most evidence was low or very low.
CONCLUSION
Adjuvant AAPs had significant efficacy compared with PBO, but treatment decisions must be made to balance the risks and benefits.
Topics: Adult; Humans; Depressive Disorder, Major; Antipsychotic Agents; Network Meta-Analysis; Quetiapine Fumarate; Aripiprazole; Olanzapine; Adjuvants, Immunologic; Adjuvants, Pharmaceutic
PubMed: 37746943
DOI: 10.1097/MD.0000000000034670 -
Current Opinion in Pharmacology Oct 2019The ability of antibiotics to cure bacterial infections is at a serious risk due to the emergence and worldwide spread of superbugs. A lack of innovation and investment... (Review)
Review
The ability of antibiotics to cure bacterial infections is at a serious risk due to the emergence and worldwide spread of superbugs. A lack of innovation and investment for almost 50 years has led to significant efforts currently being devoted to find alternative and innovative therapies to face this challenge. This short review highlights some of the recent efforts to develop synthetic small molecules with anti-infective activity. This article is focused on those compounds that, when co-administered with an antibiotic, enhance the antimicrobial action of the drug, as well as compounds that target unexplored objectives for bacterial survival. Selected examples are provided.
Topics: Adjuvants, Pharmaceutic; Anti-Bacterial Agents; Bacterial Infections; Humans
PubMed: 31005786
DOI: 10.1016/j.coph.2019.03.004