A Novel Tetravalent Bispecific Immune Cell Engager Activates Natural Killer Cells to Kill Cancer Cells without Mediating Fratricide.

We previously reported the structure, affinity, and anticancer activity of a bivalent bispecific natural killer cell engager (BiKE) composed of one anti-CD16a VHH and one anti-HER2 VHH fused via a linker. In this study, we explored the engineering of a tetravalent BiKE by fusing two anti-CD16a and two anti-HER2 VHHs in tandem, using bivalent BiKE as a template. The tetravalent BiKE was genetically engineered, and its tertiary structure was predicted using in silico modeling.

Bispecific immune cell engager enhances the anticancer activity of CD16+ NK cells and macrophages in vitro, and eliminates cancer metastasis in NK humanized NOG mice.

Background: In a prior report, we detailed the isolation and engineering of a bispecific killer cell engager, referred to as BiKE:E5C1. The BiKE:E5C1 exhibits high affinity/specificity for the CD16a activating receptor on natural killer (NK) cells and human epidermal growth factor receptor 2 (HER2) on cancer cells. In vitro studies have demonstrated that BiKE:E5C1 can activate the NK cells and induce the killing of HER2+ ovarian and breast cancer cells, surpassing the performance of the best-in-class monoclonal antibody, Trazimera (trastuzumab).

A high affinity and specificity anti-HER2 single-domain antibody (VHH) that targets trastuzumab's epitope with versatile biochemical, biological, and medical applications.

In the past decade, various single-domain antibodies from llamas, also known as VHH or nanobody, have been discovered with applications in tumor imaging and cancer therapy. However, the potential application of anti-HER2 VHHs as a diagnostic tool suitable for ELISA, flow cytometry, cell imaging, bispecific antibody engineering, and immunohistochemistry has not been fully elucidated. To investigate this potential, HER2 antigen was expressed in HEK293 F cells, purified, and used to immunize llama.

Small extracellular vesicles (sEVs): discovery, functions, applications, detection methods and various engineered forms.

Introduction: Extracellular vesicles (EVs) are cell-created delivery systems of proteins, lipids, or nucleic acids, and means of extracellular communication. Though sEVs were initially considered to be the waste disposal mechanism, today they are at the forefront of research with different biological and pathological functions. Such EVs play a key role in the immunoregulation, CNS development, nervous system physiology, mammary gland development, induction of immunosuppression in pregnancy, the developmental signaling pathways, regeneration of different tissues, inflammation, angiogenesis, coagulation, apoptosis, stem cell differentiation, and extracellular matrix turnover.

Immunotherapeutic approaches to curtail COVID-19.

COVID-19, the disease induced by the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has imposed an unpredictable burden on the world. Drug repurposing has been employed to rapidly find a cure; but despite great efforts, no drug or vaccine is presently available for treating or prevention of COVID-19. Apart from antivirals, immunotherapeutic strategies are suggested considering the role of the immune response as the host defense against the virus, and the fact that SARS-CoV-2 suppresses interferon induction as an immune evasion strategy.

In Silico Elucidation of Deleterious Non-synonymous SNPs in SHANK3, the Autism Spectrum Disorder Gene.

SHANK3, a member of SH3 and multiple ankyrin repeat domains (SHANK) proteins, plays a crucial role in synaptic development and functions. Mutations in SHANK3 have been linked to a number of neuropsychiatric and neurodevelopmental disorders, including autism spectrum disorder. In this study, the functional and structural impacts of non-synonymous single-nucleotide polymorphisms (SNPs) on SHANK3 were predicted.

Effect of alumina (AlO) nanoparticles and macroparticles on - L. in vitro cultures: assessment of growth parameters and oxidative stress-related responses.

The impact of 100 μg ml alumina (AlO) nanoparticles (NPs) on (fenugreek) in vitro cultures was studied within 3 weeks (on days 1, 7, 14, and 21) and compared with the control and bulk (macrometer-sized particles) alumina-treated groups. Transmission electron microscopy (TEM) and dynamic light scattering were used for the characterization of NPs. The results of TEM analysis represented a nearly spherical shape for the NPs with agglomeration.

Selected application of peptide molecules as pharmaceutical agents and in cosmeceuticals.

: Peptide molecules are being vastly investigated as an emerging class of therapeutic molecules in recent years. Currently, 60 peptides have been approved by the US Food and Drug Administration (FDA), and more would enter the market in near future. Peptides have already opened their ways into cosmeceutical and food industries as well.

A comprehensive in silico characterization of bacterial signal peptides for the excretory production of phenylalanine ammonia lyase in .

double mutant (C503S/C565S) phenylalanine ammonia-lyase (PAL) is an appealing enzyme in the enzyme-replacement therapy of phenylketonuria. Yet abundant production of this enzyme has been of concern for industrial production. In this study, we have characterized 1175 bacterial signal peptides (SPs) and identified the most efficient ones for the excretory production of mutant AvPAL.

A comprehensive review of signal peptides: Structure, roles, and applications.

Signal peptides (SP) are short peptides located in the N-terminal of proteins, carrying information for protein secretion. They are ubiquitous to all prokaryotes and eukaryotes. SPs have been of special interest in several scientific and industrial fields, including recombinant protein production, disease diagnosis, immunization, and laboratory techniques.

Identification and functional prediction of stress responsive AP2/ERF transcription factors in Brassica napus by genome-wide analysis.

Using homology and domain authentication, 321 putative AP2/ERF transcription factors were identified in Brassica napus, called BnAP2/ERF TFs. BnAP2/ERF TFs were classified into five major subfamilies, including DREB, ERF, AP2, RAV, and BnSoloist. This classification is based on phylogenetic analysis, motif identification, gene structure analysis, and physiochemical characterization.

Genome-wide identification, functional prediction, and evolutionary analysis of the R2R3-MYB superfamily in Brassica napus.

R2R3-MYB transcription factors (TFs) have been shown to play important roles in plants, including in development and in various stress conditions. Phylogenetic analysis showed the presence of 249 R2R3-MYB TFs in Brassica napus, called BnaR2R3-MYB TFs, clustered into 38 clades. BnaR2R3-MYB TFs were distributed on 19 chromosomes of B.