[Advances in structural design of T cell-dependent bispecific antibodies].

With the development of antibody engineering, a diverse range of structures for T cell-dependent bispecific antibodies targeting CD3 have been devised to meet the needs of various clinical therapies. T cell-dependent bispecific antibodies can be categorized into IgG-like and non-IgG-like formats based on the presence or absence of an Fc domain. The most common difficulty in manufacturing bispecific antibodies is the mispairing between light and heavy chains.

TFAB002s, novel CD20-targeting T cell-dependent bispecific Fab-FabCH3 antibodies, exhibit potent antitumor efficacy against malignant B-cell lymphoma.

B-cell lymphoma, clinically, comprises a heterogeneous group of malignancies that encompass various subtypes. CD20 is an optimal target for therapeutic antibodies in B-cell lymphoma immunotherapy since approximately 90% of B-cell malignancies typically exhibit CD20 expression on their surface, while its presence is limited in normal tissues. In this study, we have developed a series of novel non-IgG-like T cell-dependent bispecific antibodies by constructing Fab-FabCH3, referred to as Tandem Antigen-binding Fragment 002 (TFAB002), which specifically target CD20 for the treatment of malignant B-cell lymphoma.

Preparation, characterization and cytotoxic activity of selenium nanoparticles stabilized with a heteropolysaccharide isolated from Sanghuangporus vaninii residue.

Selenium nanoparticles (SeNPs) possess unique features with excellent bioavailability and bioactivity, but the poor stability limits its application. A combination of polysaccharides and SeNPs is an effective strategy to overcome the limitation. Herein, a heteropolysaccharide (SVL-3) with an average molecular weight of 2.

Soluble expression of hMYDGF was improved by strain engineering and optimizations of fermentation strategies in Escherichia coli.

Myeloid-derived growth factor (MYDGF) is a cytokine that exhibits a variety of biological functions. This study focused on utilizing BL21(DE3) strain engineering and fermentation strategies to achieve high-level expression of soluble human MYDGF (hMYDGF) in Escherichia coli. Initially, the E.

Delivery of mRNA Encoding Interleukin-12 and a Stimulator of Interferon Genes Agonist Potentiates Antitumor Efficacy through Reversing T Cell Exhaustion.

T cell exhaustion has emerged as a major hurdle that impedes the clinical translation of stimulator of interferon genes (STING) agonists. It is crucial to explore innovative strategies to rejuvenate exhausted T cells and potentiate the antitumor efficacy. Here, we propose an approach utilizing MSA-2 as a STING agonist, along with nanoparticle-mediated delivery of mRNA encoding interleukin-12 (IL-12) to restore the function of T cells.

A screening study on the detection strain of Coxsackievirus A6: the key to evaluating neutralizing antibodies in vaccines.

The increasing incidence of diseases caused by Coxsackievirus A6 (CV-A6) and the presence of various mutants in the population present significant public health challenges. Given the concurrent development of multiple vaccines in China, it is challenging to objectively and accurately evaluate the level of neutralizing antibody response to different vaccines. The choice of the detection strain is a crucial factor that influences the detection of neutralizing antibodies.

Modified response evaluation criteria in solid tumors: A better response evaluation criteria for patients with non-squamous non-small cell lung cancer after bevacizumab treatment.

Aim: Cavitation of lesions is common in non-squamous non-small cell lung cancer (non-squamous-NSCLC) patients treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFRIs). However, traditional response evaluation criteria in solid tumors (RECIST) do not take cavitation into consideration and may no longer be accurate for potentially reflecting the real clinical efficacy of anti-vessel growth therapy. Here, we aimed to optimize the traditional RECIST version 1.

Non-small cell lung cancers (NSCLCs) oncolysis using coxsackievirus B5 and synergistic DNA-damage response inhibitors.

With the continuous in-depth study of the interaction mechanism between viruses and hosts, the virus has become a promising tool in cancer treatment. In fact, many oncolytic viruses with selectivity and effectiveness have been used in cancer therapy. Human enterovirus is one of the most convenient sources to generate oncolytic viruses, however, the high seroprevalence of some enteroviruses limits its application which urges to exploit more oncolytic enteroviruses.

Advances in targeted therapy and immunotherapy for melanoma (Review).

Melanoma is the most aggressive and deadly type of skin cancer and is known for its poor prognosis as soon as metastasis occurs. Since 2011, new and effective therapies for metastatic melanoma have emerged, with US Food and Drug Administration approval of multiple targeted agents, such as V-Raf murine sarcoma viral oncogene homolog B1/mitogen-activated protein kinase kinase inhibitors and multiple immunotherapy agents, such as cytotoxic T lymphocyte-associated protein 4 and anti-programmed cell death protein 1/ligand 1 blockade. Based on insight into the respective advantages of the above two strategies, the present article provided a review of clinical trials of the application of targeted therapy and immunotherapy, as well as novel approaches of their combinations for the treatment of metastatic melanoma in recent years, with a focus on upcoming initiatives to improve the efficacy of these treatment approaches for metastatic melanoma.

Prognosis of Patients With Triple-negative Breast Cancer: A Population-based Study From SEER Database.

Background: Triple-negative breast cancer (TNBC) was a particularly aggressive subtype of breast cancer associated with poor prognosis. This retrospective study was conducted to investigate the clinical features, prognostic factors, and benefits of surgery of patients with TNBC.

Methods: From 2010 to 2015, 33654 female patients with TNBC were obtained from the Surveillance, Epidemiology, and End Results (SEER) database.

Retrospective immunogenicity analysis of seasonal flu H3N2 vaccines recommended in the past ten years using immunized animal sera.

Background: Influenza A (H3N2) virus (A/H3N2) has complex antigenic evolution, resulting in frequent vaccine strain updates. We aimed to evaluate the protective effect of the vaccine strains on the circulating strains from past ten years and provide a basis for finding a broader and more efficient A/H3N2 vaccine strain.

Methods: Eighty-four representative circulating A/H3N2 strains were selected from 65,791 deposited sequences in 2011-2020 and pseudotyped viruses were constructed with the VSV vector.

A Short 5'triphosphate RNA nCoV-L Induces a Broad-Spectrum Antiviral Response by Activating RIG-I.

Small molecular nucleic acid drugs produce antiviral effects by activating pattern recognition receptors (PRRs). In this study, a small molecular nucleotide containing 5'triphosphoric acid (5'PPP) and possessing a double-stranded structure was designed and named nCoV-L. nCoV-L was found to specifically activate RIG-I, induce interferon responses, and inhibit duplication of four RNA viruses (Human enterovirus 71, Human poliovirus 1, Huma coxsackievirus B5 and Influenza A virus) in cells.

Immunogenicity and safety of an enterovirus 71 vaccine in children aged 36-71 months: A double-blind, randomised, similar vaccine-controlled, non-inferiority phase III trial.

Background: The enterovirus 71 (EV71) vaccine produced by Wuhan Institute of Biological Products Co., Ltd. (WIBP) (B-EV71) has been given to children aged 6-35 months, and it has shown good safety, immunogenicity and efficacy.

Neutralization mechanism of a human antibody with pan-coronavirus reactivity including SARS-CoV-2.

Frequent outbreaks of coronaviruses underscore the need for antivirals and vaccines that can counter a broad range of coronavirus types. We isolated a human antibody named 76E1 from a COVID-19 convalescent patient, and report that it has broad-range neutralizing activity against multiple α- and β-coronaviruses, including the SARS-CoV-2 variants. 76E1 also binds its epitope in peptides from γ- and δ-coronaviruses.

Clinical evaluation of the lot-to-lot consistency of an enterovirus 71 vaccine in a commercial-scale phase IV clinical trial.

Objective: To evaluate the immunogenicity, safety and lot-to-lot consistency of an inactivated enterovirus 71 (EV71) vaccine cultured in bioreactors with different specifications after full immunization.

Methods: A randomized, double-blind trial was performed in 3,000 children aged 6 ~ 35 months with six vaccine batches, which were prepared in 40 L and 150 L bioreactors for three consecutive batches respectively. Children were immunized on day 0 and 28, serum samples were collected on day 0 and 56, and neutralizing antibody titers were determined by the microcytopathic method.

Migfilin: Cell Adhesion Effect and Comorbidities.

Cell adhesion manifests as cell linkages to neighboring cells and/or the extracellular matrix (ECM). Migfilin is a widely expressed adhesion protein. It comprises three LIM domains in the C-terminal region and one proline-rich sequence in the N-terminal region.

Transcriptomic analysis of the innate immune signatures of a SARS-CoV-2 protein subunit vaccine ZF2001 and an mRNA vaccine RRV.

Analysis of large-scale gene expression post vaccination can provide an overview of immune responses. We used transcriptional approaches to comprehensively analyze the innate immune response signatures elicited by protein subunit (PS) vaccine ZF2001 and an mRNA vaccine named RRV. A fine-grained time-dependent dissection of large-scale gene expression post immunization revealed that ZF001 induced MHC class II-related genes, including and , more expeditiously than the RRV.

Comparison of the neutralizing activities of antibodies in clinical sera against both Sabin and wild-type polio pseudoviruses.

The cost-effectiveness of the Sabin inactivated poliovirus vaccine derived from the Sabin strains (S-IPV) and its reduced biosecurity risks during its manufacture make it the vaccine of choice over the IPVs derived from wild-type polioviruses. However, it is difficult to evaluate whether S-IPVs can achieve wild-type poliovirus containment in China, making its development there less attractive. To facilitate the development and adoption of S-IPVs in China, the aim of this study was to develop an alternative neutralizing assay using either a polio pseudovirus derived from a Sabin strain (S-pNA) or one derived from a wild-type strain (w-pNA) to replace the conventional neutralizing assay which uses live polioviruses.

Evaluation of the cross-neutralization activities elicited by Coxsackievirus A10 vaccine strains.

Increased severity of diseases caused by Coxsackievirus A10 (CV-A10) as well as a large number of mutants and recombinants circulating in the population are a cause of concern for public health. A vaccine with broad-spectrum and homogenous protective capacity is needed to prevent outbreaks of CV-A10. Here, we evaluated cross-neutralization of prototype strain and 17 CV-A10 strains from related manufacturers in mainland China using 30 samples of plasma collected from naturally infected human adults and 18 sera samples from murine immunized with the above strains of CV-A10.

[Antigenic evolution of influenza virus and the implications for influenza vaccine development].

Influenza virus has a continuous and extensive impact on human health around the world. Its extensive animal host characteristics and highly variable characteristics lead to continuous antigen drift and change of susceptible populations, causing repeated global influenza epidemics, and also affecting the protective effect of seasonal influenza vaccine. This research in a number of subtypes of influenza a virus, for example, from the antigenic drift of antigenicity, influence of the seasonal influenza vaccine strains and popular strain compatibility, broad-spectrum flu vaccine development train of thought, etc.

Comprehensive mapping of binding hot spots of SARS-CoV-2 RBD-specific neutralizing antibodies for tracking immune escape variants.

Background: The receptor-binding domain (RBD) variants of SARS-CoV-2 could impair antibody-mediated neutralization of the virus by host immunity; thus, prospective surveillance of antibody escape mutants and understanding the evolution of RBD are urgently needed.

Methods: Using the single B cell cloning technology, we isolated and characterized 93 RBD-specific antibodies from the memory B cells of four COVID-19 convalescent individuals in the early stage of the pandemic. Then, global RBD alanine scanning with a panel of 19 selected neutralizing antibodies (NAbs), including several broadly reactive NAbs, was performed.

Effects of Maillard reaction on structural modification and potential allergenicity of peanut 7S globulin (Ara h 1).

Background: Ara h 1 is a major food allergen in peanuts. Recently, many studies have revealed that the Maillard reaction (MR) affects the allergenicity of food proteins.

Results: To investigate the influence of the MR on the allergenicity of Ara h 1, R-Ara h 1 was processed with glucose in dry heating conditions for different periods.

Establishment of a cell-based quantitative reverse transcription-polymerase chain reaction (RT-qPCR) assay for detection of multivalent rotavirus vaccine.

Because of deficiencies of traditional potency tests in rotavirus detection, a one-step TaqMan probe-based quantitative reverse transcription-polymerase chain reaction (RT-qPCR) assay combined with cell-based method was established to determine the infectious potency of the target virus in multivalent live rotavirus vaccines in vitro. Series dilutions of rotavirus samples were inoculated into Vero cells and cultured for 24 hours. The cells were lysed and the potency was detected by RT-qPCR.