Recent Advances in the Development of Monoclonal Antibodies and Next-Generation Antibodies

ImmunoHorizons, Journal Year: 2023, Volume and Issue: 7(12), P. 886 - 897

Published: Dec. 1, 2023

Abstract mAbs are highly indispensable tools for diagnostic, prophylactic, and therapeutic applications. The first technique, hybridoma technology, was based on fusion of B lymphocytes with myeloma cells, which resulted in generation single against a specific Ag. Along several novel alternative methods have been developed to improve mAb generation, ranging from electrofusion the discovery completely technologies such as cell immortalization; phage, yeast, bacterial, ribosome, mammalian display systems; DNA/RNA encoded Abs; technology; transgenic animals; artificial intelligence/machine learning. This commentary outlines evolution, methodology, advantages, limitations various production techniques. Furthermore, advent next-generation Ab single-chain variable fragments, nanobodies, bispecific Abs, Fc-engineered biosimilars, mimetics, Ab-drug conjugates, healthcare pharmaceutical sectors become resourceful develop treatments diseases cancer autoimmune infectious diseases.

Language: Английский

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Targeting Plasmodium falciparum Schizont Egress Antigen-1 in Infected Red Blood Cells: Docking-Based Fingerprinting, Density Functional Theory, Molecular Dynamics Simulations, and Binding Free Energy Analysis

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(2), P. 237 - 237

Published: Feb. 10, 2025

Background: Malaria remains a global health crisis, with the World Health Organization (WHO) reporting 241 million cases and 627,000 deaths worldwide in 2020, predominantly affecting Sub-Saharan Africa. The region accounted for 95% of 96% deaths, reflecting immense challenges malaria prevention treatment. Plasmodium falciparum Schizont Egress Antigen-1 (PfSEA-1) is crucial facilitating immune evasion promoting sequestration infected red blood cells (RBCs), contributing to severe symptoms, including cerebral malaria, necessitates urgent identification novel or repurposed drugs targeting PfSEA1. Methods: protein structure PfSEA-1 (UniProt ID: A0A143ZXM2) was modelled three dimensions, prepared, subjected 50 ns molecular dynamics (MD) simulation achieve stable structure. equilibrated minimised docking against DrugBank compound library. Docking analysis identified potential inhibitors, Alparabinos, Dihycid, Ambenzyne, Amiflupipquamine, Ametchomine, Chlobenethyzenol, scores ranging from −8.107 −4.481 kcal/mol. Advanced analyses such as interaction fingerprints, density functional theory (DFT), pharmacokinetics evaluations were conducted. Finally, 100 MD NPT ensemble performed assess stability protein–ligand complexes, binding free energy total calculations derived trajectories. Results Discussion: compounds exhibited satisfactory pharmacokinetic profiles interactions PfSEA-1. simulations demonstrated overall stability, minor fluctuations some instances. Key intermolecular observed, supporting compounds. Binding confirmed favourable interactions, underscoring their therapeutic agents falciparum. While silico results are promising, experimental validation essential confirm efficacy safety clinical use. Conclusion: These findings highlight promising antimalarial target identify inhibitors strong affinities pharmacokinetics. computational encouraging, further vitro vivo necessary facilitate future drug development.

Language: Английский

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Plasmodium falciparum and immune phagocytosis: characterization of the process

Immunology and Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Abstract Phagocytosis is a critical immunological process that enables the immune system to recognize and eliminate foreign pathogens self‐derived pathogenic molecules. Improving overall understanding of this mechanism during malarial infection imperative. The mechanisms by which phagocytosis eradicates malaria parasites, particularly Plasmodium falciparum , remain incompletely understood warrant further investigation. In context, previous studies have shown various factors such as phagocyte cell subclasses, plasma protein molecules evasion tactics influence phagocytic differently. However, underlying activity P. infections are still ambiguous. review, we summarize key aspects current knowledge infection. We highlight significant involvement distinct active cells induce phagocytosis. Additionally, discuss implications potential therapeutic approaches enhance its effectiveness.

Language: Английский

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Escaping the enemy’s bullets: an update on how malaria parasites evade host immune response

Parasitology Research, Journal Year: 2023, Volume and Issue: 122(8), P. 1715 - 1731

Published: May 23, 2023

Abstract Malaria continues to cause untold hardship inhabitants of malaria-endemic regions, causing significant morbidity and mortality that severely impact global health the economy. Considering complex life cycle malaria parasites (MPs) biology, continued research efforts are ongoing improve our understanding pathogenesis diseases. Female Anopheles mosquito injects MPs into its hosts during a blood meal, invade host skin hepatocytes without any serious symptoms. Symptomatic infections occur only erythrocytic stage. In most cases, host’s innate immunity (for malaria-naïve individuals) adaptive pre-exposed mount severe attacks destroy MPs. It is increasingly understood have developed several mechanisms escape from immune destruction. This review presents recent knowledge on how system destroys invading as well survival or evasion mechanisms. On invasion cells, release molecules bind cell surface receptors reprogram in way lose capacity them. also hide cells by inducing clustering both infected uninfected erythrocytes (rosettes), endothelial activation. We hope this will inspire more provide complete biology promote interventions eradicate notorious disease.

Language: Английский

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Leishmaniasis y su Resistencia a Fármacos: Un Enfoque Bibliométrico

Estudios y Perspectivas Revista Científica y Académica, Journal Year: 2025, Volume and Issue: 4(4), P. 2464 - 2512

Published: Jan. 22, 2025

El desarrollo de resistencia a los fármacos leishmanicidas representa un reto significativo en el control la leishmaniasis, debido disminución eficacia tratamientos por aparición cepas resistentes. Este estudio tuvo como objetivo analizar las tendencias investigación relacionadas con farmacorresistencia Leishmania, identificando patrones literatura producción científica, autores relevantes y actuales. Se revisaron 672 artículos indexados dos principales bases datos fuentes bibliográficas, posteriormente fueron clasificados, siguiendo metodología PRISMA. En presente trabajo se plantean dar respuestas siguientes interrogantes: 1. ¿Explorar medidas bibliométricas estudios Leishmaniasis su Fármacos? 2. ¿Cuáles son fármacos?, aplicando análisis bibliométrico. Los resultados obtenidos definen 4 áreas críticas fármacos, son: Enfermedades Tropicales Descubrimiento Fármacos, Resistencia Terapéutica Leishmaniasis, Dinámica Molecular Actividad Antileishmanial Simulación Cribado Molecular.

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State-of-the-art Review on the Antiparasitic Activity of Benzimidazolebased Derivatives: Facing Malaria, Leishmaniasis, and Trypanosomiasis

Current Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 31(15), P. 1955 - 1982

Published: Sept. 18, 2023

Abstract: Protozoan parasites represent a significant risk for public health worldwide, afflicting particularly people in more vulnerable categories and cause large morbidity heavy economic impact. Traditional drugs are limited by their toxicity, low efficacy, route of administration, cost, reflecting priority global management. Moreover, the drug resistance phenomenon threatens positive therapy outcome. This scenario claims need addressing adequate therapies. Among diverse strategies implemented, medicinal chemistry efforts have also focused attention on benzimidazole nucleus as promising pharmacophore generation new candidates. Hence, present review provides insight into recent progress benzimidazole-based derivatives discovery against important protozoan diseases, such malaria, leishmaniasis trypanosomiasis. The relevant chemical features structure-activity relationship studies these molecules discussed purpose paving way towards development viable treatment parasitic infections.

Language: Английский

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Plant-based nanoparticles targeting malaria management

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 9, 2024

Malaria is one of the most devastating diseases across globe, particularly in low-income countries Sub-Saharan Africa. The increasing incidence malaria morbidity mainly due to shortcomings preventative measures such as lack vaccines and inappropriate control over parasite vector. Additionally, high mortality rates arise from therapeutic failures poor patient adherence drug resistance development. Although causative pathogen (

Language: Английский

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Biogenically synthesized green silver nanoparticles exhibit antimalarial activity

Discover Nano, Journal Year: 2024, Volume and Issue: 19(1)

Published: Aug. 31, 2024

The suboptimal efficacies of existing anti-malarial drugs attributed to the emergence drug resistance dampen clinical outcomes. Hence, there is a need for developing novel and targets. Recently silver nanoparticles (AgNPs) constructed with leaf extracts Euphorbia cotinifolia were shown possess antimalarial activity. Therefore, synthesized AgNPs from (EcAgNPs) tested their parasite clearance We determined activity in asexual blood stage infection 3D7 (laboratory strain) P. falciparum. EcAgNPs demonstrated significant inhibition growth (EC50 0.75 µg/ml) routine vitro culture seen induce apoptosis falciparum through increased reactive oxygen species (ROS) ROS production activated programmed cell death pathways characterized by caspase-3 calpain Also, altered transcriptional regulation Bax/Bcl-2 ratio indicated enhanced apoptosis. Moreover, inhibited expression PfLPL-1 suggestive dysregulated host fatty acid flux via lipid storage. Overall, our findings suggest that are non-toxic targeted treatment, could be promising therapeutic approach clearing malaria infection.

Language: Английский

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A broadly cross-reactive i-body to AMA1 potently inhibits blood and liver stages of Plasmodium parasites

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 22, 2024

Apical membrane antigen-1 (AMA1) is a conserved malarial vaccine candidate essential for the formation of tight junctions with rhoptry neck protein (RON) complex, enabling Plasmodium parasites to invade human erythrocytes, hepatocytes, and mosquito salivary glands. Despite its critical role, extensive surface polymorphisms in AMA1 have led strain-specific protection, limiting success AMA1-based interventions beyond initial clinical trials. Here, we identify an i-body, humanised single-domain antibody-like molecule that recognises pan-species conformational epitope low nanomolar affinity inhibits binding RON2 ligand AMA1. Structural characterisation indicates WD34 i-body spans centre hydrophobic cleft AMA1, where interacting residues are highly among all species. Furthermore, show merozoite invasion erythrocytes by multiple species hepatocyte P. falciparum sporozoites. short half-life mouse serum, demonstrate transiently suppressed berghei infections female BALB/c mice. Our work describes first biologic inhibitory activity against life-cycle stages Plasmodium. With improved pharmacokinetic characteristics, could be potential immunotherapy important parasite invasion, but hamper antibody development. Here authors molecule, binds examined invasion.

Language: Английский

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LEVERAGING THE SUCCESS OF MRNA LIPID NANOPARTICLE VACCINE IN COVID-19 TREATMENT: A NARRATIVE REVIEW ON ITS POTENTIAL APPLICATION IN MALARIA TREATMENT

International Journal of Applied Pharmaceutics, Journal Year: 2024, Volume and Issue: unknown, P. 59 - 66

Published: June 7, 2024

Malaria, which is caused by the Plasmodium parasite and transmitted mosquitoes, continues to be a major global health issue. The worldwide community work toward finding conclusive answer malaria problem, but it still elusive. Developing successful vaccine has proven difficult due parasite’s complicated life cycle ability change develop resistance interventions rapidly. Amidst this backdrop, advent of mRNA Lipid Nanoparticle (mRNA-LNP) vaccines, exemplified their resounding success in mitigating Coronavirus Disease 2019 (COVID-19) pandemic, kindled newfound hope development. This review examines potential leveraging technology induce robust immune response, thereby potentially revolutionising landscape prevention through development breakthrough vaccines. intricate interplay between efficacy mRNA-LNP against COVID-19 its prospective utility addressing also deliberated upon.

Language: Английский

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