Superantigen-fused T cell engagers for tumor antigen-mediated robust T cell activation and tumor cell killing.

Inadequate T cell activation has severely limited the success of T cell engager (TCE) therapy, especially in solid tumors. Enhancing T cell activity while maintaining the tumor specificity of TCEs is the key to improving their clinical efficacy. However, currently, there needs to be more effective strategies in clinical practice.

Development of a Recombinant RBD Subunit Vaccine for SARS-CoV-2.

The novel coronavirus pneumonia (COVID-19) pandemic is a great threat to human society and now is still spreading. Although several vaccines have been authorized for emergency use, only one recombinant subunit vaccine has been permitted for widespread use. More subunit vaccines for COVID-19 should be developed in the future.

Optimization strategies for expression of a novel bifunctional anti-PD-L1/TGFBR2-ECD fusion protein.

The novel anti-PD-L1/TGFBR2-ECD fusion protein (BR102) comprises an anti-PD-L1 antibody (HS636) which is fused at the C terminus of the heavy chain to a TGF-β1 receptor Ⅱ ectodomain (TGFBR2-ECD), and which can sequester the PD-1/PD-L1 pathway and TGF-β bioactivity in the immunosuppressive tumor microenvironment. In the expression of TGFBR2-ECD wild-type fused protein (BR102-WT), a 50 kDa clipped species was confirmed to be induced by proteolytic cleavage at a "QKS" site located in the N-terminus of the ectodomain, which resulted in the formation of IgG-like clipping. The matrix metalloproteinase-9 was determined to be associated with BR102-WT digestion.

Microvessel Density: Integrating Sex-Based Differences and Elevated Cardiovascular Risks in Metabolic Syndrome.

Metabolic syndrome (MetS) is a complex pathological state consisting of metabolic risk factors such as hypertension, insulin resistance, and obesity. The interconnectivity of cellular pathways within various biological systems suggests that each individual component of MetS may share common pathological sources. Additionally, MetS is closely associated with vasculopathy, including a reduction in microvessel density (MVD) (rarefaction) and elevated risk for various cardiovascular diseases.

Soluble Expression of Fc-Fused T Cell Receptors Allows Yielding Novel Bispecific T Cell Engagers.

The specific recognition of T cell receptors (TCR) and peptides presented by human leukocyte antigens (pHLAs) is the core step for T cell triggering to execute anti-tumor activity. However, TCR assembly and soluble expression are challenging, which precludes the broad use of TCR in tumor therapy. Herein, we used heterodimeric Fc to assist in the correct assembly of TCRs to achieve the stable and soluble expression of several TCRs in mammalian cells, and the soluble TCRs enable us to yield novel bispecific T cell engagers (TCR/aCD3) through pairing them with an anti-CD3 antibody.

Specific Inhibition of Tumor Growth by T Cell Receptor-Drug Conjugates Targeting Intracellular Cancer-Testis Antigen NY-ESO-1/LAGE-1.

Despite the significant therapeutic advances in T-cell immunotherapy, many malignancies remain unresponsive, which might be because of the negative regulation of T cells by the tumor microenvironment (TME). T cells discriminate tumor cells and normal cells through T-cell receptors (TCRs); therefore, we generated a novel type of TCR-drug conjugates (TDCs) by referring antibody-drug conjugations (ADCs) to overcome the effects of the TME on T cells while preserving the specificity of TCR for tumor recognition. We selected HLA-A2/NY-ESO-1 (peptide NY-ESO-1 in complex with human leukocyte antigen serotype HLA-A*02:01) as the antigen and the antigen-specific TCR (1G4113) as the carrier.

The Antitumor Activity of TCR-Mimic Antibody-Drug Conjugates (TCRm-ADCs) Targeting the Intracellular Wilms Tumor 1 (WT1) Oncoprotein.

Wilms tumor 1 (WT1) oncoprotein is an intracellular oncogenic transcription factor which is barely expressed in normal adult tissues but over expressed in a variety of leukemias and solid cancers. WT1-derived HLA-A*02:01 T cell epitope, RMFPNAPYL (RMF), is a validated target for T cell-based immunotherapy. We generated two T cell receptor mimic antibody-drug conjugates (TCRm-ADCs), ESK-MMAE, and Q2L-MMAE, against WT1 RMF/HLA-A*02:01 complex with distinct affinities, which mediate specific antitumor activity.

Meta-analysis and systematic review of the efficacy and resistance for human immunodeficiency virus type 1 integrase strand transfer inhibitors.

Integrase strand transfer inhibitors (INSTIs) are the most recent class of antiretroviral drugs with potent and durable antiviral activity used to treat human immunodeficiency virus type 1 (HIV-1) infection. However, development of drug resistance increases the risk of treatment failure, disease progression and mortality. A better understanding of drug efficacy and resistance against INSTIs is crucial for their efficient use and the development of new antiretrovirals.

Associations between human leukocyte antigen polymorphisms and hypersensitivity to antiretroviral therapy in patients with human immunodeficiency virus: a meta-analysis.

Background: Human leukocyte antigen (HLA) alleles are implicated in drug-induced hypersensitivity, including by nevirapine and abacavir. The purpose of this meta-analysis was to evaluate the relationship between HLA polymorphisms and hypersensitivity to antiretroviral therapy in human immunodeficiency virus (HIV)-infected patients.

Methods: We conducted a systematic search of PubMed, Embase, Web of Science, and the Cochrane Library for studies that evaluated the associations of HLA polymorphisms with antiretroviral therapy-induced hypersensitivity published in April 2019.

MicroRNA-2738 regulates gene expression in the sex determination pathway in Bombyx mori.

MicroRNAs (miRNAs) are a class of short, non-coding transcripts that bind to 3'-untranslated regions to trigger messenger RNA degradation or translational inhibition. Here we explored how miRNAs regulate sex determination in Bombyx mori, a lepidopteran model insect. Genes known to be involved in sex determination, BmPSI, Bmdsx, and BmMasc, are predicted targets of the species-specific miR-2738.

Influence of OATP1B1 and OATP1B3 mutations and glomerular filtration rate on trough serum digoxin concentration in the Chinese population: A prospective cohort study.

Polymorphisms of organic anion transporting polypeptides (OATPs) have been reported to affect trough serum digoxin concentration (SDC). However, the association of these polymorphisms with trough SDC in Chinese heart failure patients has not been studied. We aim to explore whether OATP1B1 388A>G, OATP1B1 521T>C, and OATP1B3 699G>A influence trough SDC in Chinese heart failure patients and to make clinical recommendations.

Osteological Re-Assessment and Taxonomic Revision of "Tanius laiyangensis" (Ornithischia: Hadrosauroidea) from the Upper Cretaceous of Shandong, China.

Tanius is the earliest named ornithischian genus from China. Since 1929, three species of this genus, namely T. sinensis (the type species), "T.

Identification of a germline-expression promoter for genome editing in Bombyx mori.

Identification of stage- and tissue-specific cis-regulatory elements will enable more precise genomic editing. In previous studies of the silkworm Bombyx mori, we identified and characterized several tissue- and sex-specific cis-regulatory elements using transgenic technology, including a female- and fat body-specific promoter, vitellogenin, testis-specific promoters, Radial spoke head 1 (BmR1) and beta-tubulin 4 (Bmβ4). Here we report a cis-regulatory element specific for a somatic and germ cell-expressed promoter, nanos (Bmnos).

Genetic Polymorphisms and In Silico Mutagenesis Analyses of CYP2C9, CYP2D6, and CYPOR Genes in the Pakistani Population.

Diverse distributions of pharmacogenetically relevant variants of highly polymorphic CYP2C9, CYP2D6 and CYPOR genes are responsible for some varied drug responses observed across human populations. There is limited data available regarding the pharmacogenetic polymorphisms and frequency distributions of major allele variants in the Pakistani population. The present in silico mutagenesis study conducted on genotype pharmacogenetic variants and comparative analysis with a global population aims to extend the currently limited pharmacogenetic available evidence for the indigenous Pakistani population.

Association between SLCO1B1 T521C polymorphism and risk of statin-induced myopathy: a meta-analysis.

Numerous studies have illustrated the relationship between SLCO1B1 T521C polymorphism and statin-induced myopathy risk; however, this association is not consistent. Three electronic databases (PubMed, EMBASE, and the Cochrane Library) were searched from inception to October 2017 to identify potential studies. The summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated from different genetic models by using a random-effects model.

Elimination of melanoma by sortase A-generated TCR-like antibody-drug conjugates (TL-ADCs) targeting intracellular melanoma antigen MART-1.

Most tumor-associated proteins are located inside tumor cells and thus are not accessible to current marketed therapeutic monoclonal antibodies or their cytotoxic conjugates. Human leukocyte antigen (HLA) class I can present peptides derived from intracellular tumor-associated proteins and somatically mutated proteins on the cell's surface, forming an HLA/peptide complex as tumor-specific antigens for T cell receptor (TCR) recognition. Therefore, HLA-mediated presentation of intracellular tumor antigen peptides provides a viable way to distinguish tumor cells from normal cells, which is important for broadening antigen selection, especially for antibody-drug conjugates (ADCs) regarding their highly cytotoxic payload.

In situ quantitative bioanalysis of monomethyl auristatin E-conjugated antibody-drug conjugates by flow cytometry.

Antibody-drug conjugates (ADCs) consist of cytotoxic agents covalently conjugated to monoclonal antibodies that substantially improve antitumour activity and reduce systemic toxicity. With the growing number of ADCs in clinical applications, more accurate bioanalysis data are urgently needed to facilitate the development and rational use of ADCs. Herein, we used antigen-positive cells as antigen carriers and ofatumumab (OFA-HL) and ofatumumab-based ADC (OFA-HL-MMAE) as examples to establish a new ligand-binding assay (LBA) method based on flow cytometry.

Neuroprotective Effects and Mechanisms of Tea Bioactive Components in Neurodegenerative Diseases.

As the population ages, neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD) impose a heavy burden on society and families. The pathogeneses of PD and AD are complex. There are no radical cures for the diseases, and existing therapeutic agents for PD and AD have diverse side effects.

Construction and application of an electrochemical biosensor based on an endotoxin aptamer.

An electrochemical biosensor that used an aptamer as a biological element was constructed to detect endotoxin. Biolayer interferometry was used to obtain the affinity constant of an aptamer for lipopolysaccharide, which had an equilibrium dissociation constant of 22.9 nM.

Pharmacogenomics of Drug Metabolizing Enzymes and Transporters: Relevance to Precision Medicine.

The interindividual genetic variations in drug metabolizing enzymes and transporters influence the efficacy and toxicity of numerous drugs. As a fundamental element in precision medicine, pharmacogenomics, the study of responses of individuals to medication based on their genomic information, enables the evaluation of some specific genetic variants responsible for an individual's particular drug response. In this article, we review the contributions of genetic polymorphisms to major individual variations in drug pharmacotherapy, focusing specifically on the pharmacogenomics of phase-I drug metabolizing enzymes and transporters.

A Tumor-Specific Neo-Antigen Caused by a Frameshift Mutation in BAP1 Is a Potential Personalized Biomarker in Malignant Peritoneal Mesothelioma.

Malignant peritoneal mesothelioma (MPM) is an aggressive rare malignancy associated with asbestos exposure. A better understanding of the molecular pathogenesis of MPM will help develop a targeted therapy strategy. Oncogene targeted depth sequencing was performed on a tumor sample and paired peripheral blood DNA from a patient with malignant mesothelioma of the peritoneum.

[Preparation of rabbit monoclonal antibody against cGMP and development of competitive ELISA for cGMP].

Objective: To prepare rabbit monoclonal antibody (RabMab) against guanosine 3', 5'-cyclic monophosphate (cGMP) and to develop a competitive ELISA for the detection of cGMP.

Methods: New Zealand white rabbits were immunized with synthesized cGMP-keyhole limpet hemoeyanin (cGMP-KLH) to prepared a RabMAb with monoclonal antibody technique of Epitomics. A competitive ELISA kit was produced with cGMP RabMAb.