Search

Copyright of Chinese Journal of Lung Cancer is the property of Chinese Journal of Lung Cancer and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In recent years, research on immunotherapy has made great progress. Currently, immunotherapy has made significant breakthrough, especially programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) checkpoint inhibitors (e.g, Nivolumab, Pembrolizumab, Atezolizumab, Durvalumab and Avelumab, etc.) have brought clinical benefits to patients with various pathological types of lung cancer, including squamous cell carcinoma, adenocarcinoma and small cell lung cancer. In this paper, the application value and current status of PD-1/PD-L1 checkpoint inhibitors in lung cancer were comprehensively analyzed by reviewing and interpreting representative clinical studies. Based on the results of various large-scale clinical trials results, the indications of immunotherapy in lung cancer have been continuously broadened, and the details of immunotherapy have also been constantly optimized. However, immunotherapy still faces many challenges, such as the selection of immune combination strategies, the exploration of biomarkers, the management of adverse events, the feasibility of application of driver gene mutation population and so on. In this article, we made a systematic review about the latest progress of PD-1/ PD-L1 checkpoint inhibitors in lung cancer, in order to provide cutting-edge reference for the clinical workers. [ABSTRACT FROM AUTHOR]

The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and programmed death receptor 1 (PD-1)/programmed death ligand 1 (PD-L1) immune checkpoint inhibitors were landmarks in the treatment of non-small cell lung cancer (NSCLC). However, the regulation mechanisms of PD-L1 expression were not fully clear in NSCLC patients with EGFR mutations. Multiple signaling pathways may be involved in the tumorigenesis regulation. This paper summarized and reviewed the potential EGFR mutations impacting on PD-L1 expression with aims to the development of strategies on immunochemical therapy for NSCLC. [ABSTRACT FROM AUTHOR]

The negative selection algorithm (NSA) is an important detector generation algorithm for artificial immune systems. In high-dimensional space, antigens (data samples) distribute sparsely and unevenly, and most of them reside in low-dimensional subspaces. Therefore, traditional NSAs, which randomly generate detectors without considering the distribution of the antigens, cannot effectively distinguish them. To overcome this limitation, the antigen space density based real-value NSA (ASD-RNSA) is proposed in this paper. The ASD-RNSA contains two new processes. First, in order to improve detection efficiency, ASD-RNSA utilizes the antigen space density to calculate the low-dimensional subspaces where antigens are densely gathered and directly generate detectors in these subspaces. Second, to eliminate redundant detectors and prevent the algorithm from prematurely converging in high-dimensional space, ASD-RNSA suppresses candidate detectors that are recognized by other mature detectors and adopts an “ antibody suppression rate ” to replace the “ expected coverage ” as the termination condition. Experimental results show that ASD-RNSA achieves a better detection rate and has better generation quality than classical real-value NSAs. [ABSTRACT FROM AUTHOR]

Abstract: This paper describes the development of an in vitro assay to replace in vivo potency testing for the batch release of inactivated Newcastle Disease virus vaccines. The assay involves the extraction of inactivated antigen from oil emulsion vaccines, the most common adjuvant for poultry vaccines. An enzyme-linked immunosorbent assay (ELISA) is used to quantify the hemagglutinin-neuraminidase (HN) protein of the virus, which was demonstrated to correlate with protection levels. Validation experiments showed that the method could be used for HN antigen regardless of virus strain or method of inactivation. From the results of these tests it was concluded that this method could replace the in vivo methods that were prescribed in European Pharmacopoeia (Ph. Eur.) Monograph 0870 on inactivated Newcastle Disease vaccines. Large quantities of the necessary reagents and reference materials were prepared and tested. The materials were subjected to stability studies to demonstrate their suitability for long-term storage in order to guarantee long-term availability to the international community. A study in three laboratories demonstrated a good correlation of the candidate assay with two existing in vivo assays, good transferability of the assay, and excellent reproducibility of the proposed assay. A collaborative study was organized by the European Directorate for the Quality of Medicines & Healthcare (EDQM) to demonstrate the repeatability and the reproducibility of the candidate in vitro assay. The suitability of the reference reagent as a Ph. Eur. Biological Reference Preparation was also determined. Fourteen laboratories participated in this study. As a result of these efforts, the assay was included in the relevant Ph. Eur. monograph (01/2007:0870). This paper will address not only the technical aspect of this process but also factors that are considered critical for the success of this project. [Copyright &y& Elsevier]

Lipid–polymer hybrid nanoparticles (NPs), consisting of a polymeric core and a lipid shell, have been intensively examined as delivery systems for cancer drugs, imaging agents, and vaccines. For applications in vaccine particularly, the hybrid NPs need to be able to protect the enclosed antigens during circulation, easily be up-taken by dendritic cells, and possess good stability for prolonged storage. However, the influence of lipid composition on the performance of hybrid NPs has not been well studied. In this study, we demonstrate that higher concentrations of cholesterol in the lipid layer enable slower and more controlled antigen release from lipid–poly(lactide-co-glycolide) acid (lipid–PLGA) NPs in human serum and phosphate buffered saline (PBS). Higher concentrations of cholesterol also promoted in vitro cellular uptake of hybrid NPs, improved the stability of the lipid layer, and protected the integrity of the hybrid structure during long-term storage. However, stabilized hybrid structures of high cholesterol content tended to fuse with each other during storage, resulting in significant size increase and lowered cellular uptake. Additional experiments demonstrated that PEGylation of NPs could effectively minimize fusion-caused size increase after long term storage, leading to improved cellular uptake, although excessive PEGylation will not be beneficial and led to reduced improvement. Statement of Significance This paper reports the engineering of the lipid layer that encloses a polymeric nanoparticle, which can be used as a carrier for drug and vaccine molecules for targeted delivery. We demonstrated that the concentration of cholesterol is critical for the stability and uptake of the hybrid nanoparticles by dendritic cells, a targeted cell for the delivery of immune effector molecules. However, we found that hybrid nanoparticles with high cholesterol concentration tend to fuse during storage resulting in larger particles with decreased cellular uptake. This problem is subsequently solved by PEGylating the hybrid nanoparticles. With increased research and clinical applications of lipid–polymer hybrid nanoparticles in drug and vaccine delivery, this work will significantly impact the design of the hybrid nanoparticles for minimized molecule release during circulation and increased bioavailability of the target molecules. [ABSTRACT FROM AUTHOR]

Copyright of Salud Uninorte is the property of Fundacion Universidad del Norte and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Biomédica: Revista del Instituto Nacional de Salud is the property of Instituto Nacional de Salud of Colombia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: This paper proposed an improved adaptive artificial immune system (IA-AIS) for complex optimization problems in continuous search space. In this IA-AIS optimization, several operators are improved or revised which aim at faster convergence speed and better optimal solution. Further speaking, cloning and reproduction of each offspring candidate antibody are proportional to the power of its parent affinity from the antigen; while mutation of each offspring candidate antibody is inversely exponentially determined by its parent affinity from the antigen. Also, suppression operator between antibodies is dynamically controlled according to their concentration. In other words, the suppression level is proportional to their Euclidian distance in continuous search space. The effectiveness of these improvements of operators is experimentally verified. Furthermore, comparative investigations are carried out between the proposed IA-AIS optimization and other optimization utilities. Finally a persuasive case about the proportional-integral-differential (PID) controller tuning demonstrates the potential searching capability and practical value of IA-AIS optimization. [Copyright &y& Elsevier]

Abstract: Biologics are usually produced from live organisms, and the manufacturing process often involves a degree of natural variability. Characterization of biologics such as vaccines is inherently difficult due to the complex molecular structure of the antigens they contain and the presence of excipients such as preservatives and adjuvants that can interfere with testing. Therefore, each batch, lot, or serial produced must be tested before market release to ensure that the product complies with regulatory standards. This batch release testing emphasizes quality control of the final product and may be characterized by an extensive use of laboratory animals. The consistency approach is based upon the principle that the quality of a biologic is the result of the strict application of a quality system and consistent production. Subsequent batches are determined to be similar to clinically evaluated batches and therefore acceptable for release through the in-process testing that comprises this quality system. The European Centre for Validation of Alternative Methods (ECVAM) organized international workshops in 2006 and 2010 to discuss the consistency approach and its potential to reduce the number of animals used in testing of biological products. This paper provides an overview of these workshops. [Copyright &y& Elsevier]

Abstract: Hepatitis B vaccine (Engerix B) is a recombinant vaccine containing hepatitis B surface antigen (HBsAg) produced in Saccharomyces cerevisiae. Initially, this vaccine was released using specifications that required an in vivo potency assay in mice. This paper describes the move from the in vivo potency test toward in vitro potency assays: the in vitro Auszyme test (Abbott Laboratories) and the GSK Biologicals in-house test based upon the inhibition enzyme-linked immunosorbent assay (ELISA) principle. The challenges and difficulties during the development and introduction of this in vitro assay are presented from validation studies performed by GSK Biologicals, through regulatory acceptance, to the implementation of the alternative method by the European Directorate for the Quality of Medicines (EDQM) and HealthCare Control Authorities for Official batch release. Based upon our experience introducing an in vitro model for Engerix B potency assay, we offer suggestions to facilitate future introduction of in vitro assays. [Copyright &y& Elsevier]

Abstract: Veterinary vaccines must be safe, pure, potent, and effective. Potency tests help ensure that each consistently manufactured batch of vaccine provides a level of protection as determined in the original efficacy study throughout the products shelf life. Currently approved assays range from host animal vaccination and challenge to the quantification of specific protective antigens using in vitro technology. The development, maintenance, and update of in vitro potency assays continue to be a priority for both the animal health industry and the corresponding regulatory agencies. New assay development emphasis is being placed on assays that currently involve laboratory animal vaccination/challenge such as vaccines containing the Leptospira and Clostridium spp. antigens. This paper provides an overview of various in vitro potency assays available, the factors that can impact the accuracy of these methods, and specific considerations to be taken into account during assay development. [Copyright &y& Elsevier]

Artificial immune systems (AIS) have become popular among researchers and have been applied to a variety of tasks. Developing supervised learning algorithms based on metaphors from the immune system is still an area in which there is much to explore. In this paper a novel supervised immune algorithm based on clonal selection framework is proposed. It evolves a population of linear classifiers used to construct a set of classification rules. Aggregating strategies, such as bagging and boosting, are shown to work well with the proposed algorithm as the base classifier. [ABSTRACT FROM AUTHOR]

Abstract: This paper aims at developing novel bioactive fibrous mats for protein immobilization and for protein separation/purification. For this purpose, an amphiphilic triblock copolymer, biotinylated poly(ethylene glycol)-b-poly(l-lactide)-b-poly(l-lysine) was co-electrospun together with poly(l-lactide-co-glycolide) into ultrafine fibers ∼2μm in diameter, and a layer of blocking agent was coated on the fiber surfaces to block off possible non-specific binding of proteins. The biotin species retained their ability to specifically recognize and bind streptavidin, and the immobilized streptavidin could further combine with biotinylated antibodies, antigens and other biological moieties. Horseradish peroxidase-labeled streptavidin and fluorescein isothiocyanate-labeled goat globulin were used to detect the immobilizations of streptavidin and rabbit anti-goat IgG(H+L) via enzyme-linked immunoassay and confocal laser scanning microscope, respectively. The immobilized antigen was eluted from the fiber substrate with a glycine/HCl solution and the eluted antigen retained its bioactivity. Therefore, these biotin-carrying composite fibers have a variety of uses, including selective immobilization of functional proteins, antigen/antibody separation and purification, and vaccine preparation. [Copyright &y& Elsevier]

T cells recognize protein antigens as short peptides processed and displayed by antigen-presenting cells. However, the mechanism of peptide selection is incompletely understood, and, consequently, the differences in the immunogenicity of protein antigens remain largely unpredictable and difficult to manipulate. In this paper we show that the susceptibility of protein antigens to lysosomal proteolysis plays an important role in determining immunogenicity in vivo. We compared the immunogenicity of proteins with the same sequence (same T cell epitopes) and structure (same B cell epitopes) but with different susceptibilities to lysosomal proteolysis. After immunizing mice with each of the proteins adsorbed onto aluminum hydroxide as adjuvant, we measured serum IgG responses as a physiological measure of the antigen's ability to be presented on major histocompatibility complex class II molecules and to prime CD4+ T cells in vivo. For two unrelated model antigens (RNase and horseradish peroxidase), we found that only the less digestible forms were immunogenie, inducing far more efficient T cell priming and antibody responses. These findings suggest that stability to lysosomal proteolysis may be an important factor in determining immunogenicity, with potential implications for vaccine design. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii is a persistent protozoan parasite capable of infecting almost any warm-blooded vertebrates. SAG1 (p30) is the prototypic member of a superfamily of surface antigens called SRS (SAG1-related sequence). It constitutes the most abundant and predominant antigen. In this paper the primary structure of mature SAG1 gene of an Indonesian T. gondii isolate is described and sequence comparison is made with published sequence data of 7 other strains or isolates. Sequence comparison indicated that SAG1 is highly conserved through evolution and despite parasite spreading world-wide. Sequences may be divided into two major families, independent of the strain/isolate geographic origin. Variations were mainly localized at the C-terminal half or domain 2 and some clustered in restricted areas. Sequence comparison allowed us to define the Indonesian isolate as genuine virulent RH strain. A phylogenetic tree of Toxoplasma strains/isolates was constructed based on SAG1. [ABSTRACT FROM AUTHOR]