RESUMO
The biotechnological development of monoclonal antibodies and their immunotherapeutic use in oncology have grown exponentially in the last decade, becoming the first-line therapy for some types of cancer. Their mechanism of action is based on the ability to regulate the immune system or by interacting with targets that are either overexpressed in tumor cells, released into the extracellular milieu or involved in processes that favor tumor growth. In addition, the intrinsic characteristics of each subclass of antibodies provide specific effector functions against the tumor by activating antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and antibody-dependent cellular phagocytosis, among other mechanisms. The rational design and engineering of monoclonal antibodies have improved their pharmacokinetic and pharmacodynamic features, thus optimizing the therapeutic regimens administered to cancer patients and improving their clinical outcomes. The selection of the immunoglobulin G subclass, modifications to its crystallizable region (Fc), and conjugation of radioactive substances or antineoplastic drugs may all improve the antitumor effects of therapeutic antibodies. This review aims to provide insights into the immunological and pharmacological aspects of therapeutic antibodies used in oncology, with a rational approach at molecular modifications that can be introduced into these biological tools, improving their efficacy in the treatment of cancer.
Assuntos
Neoplasias , Humanos , Neoplasias/imunologia , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Animais , Imunoterapia/métodos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/imunologia , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/farmacologia , Citotoxicidade Celular Dependente de Anticorpos/imunologiaRESUMO
Two Gram-stain-positive bacterial strains, EXRC-4A-4T and RC-2-3T, were isolated from soil samples collected at Union Glacier, Antarctica. Based on 16S rRNA gene sequence similarity, strain EXRC-4A-4T was identified as belonging to the genus Rhodococcus, and strain RC-2-3T to the genus Pseudarthrobacter. Further genomic analyses, including average nucleotide identity and digital DNA-DNA hybridization, suggested that these strains represent new species. Strain EXRC-4A-4T exhibited growth at temperatures ranging from 4 to 28 °C (optimum between 20 and 28 °C), at pH 5.0-9.0 (optimum, pH 6.0), and in the presence of 0-5.0% NaCl (optimum between 0 and 1% NaCl). Strain RC-2-3T grew at 4-28 °C (optimum growth at 28 °C), pH 6.0-10 (optimum, pH 7.0) and in the presence of 0-5.0% NaCl (optimum, 1% NaCl). The fatty acid profile of EXRC-4A-4T was dominated by C17:1 ω-7, while that of RC-2-3T was dominated by anteiso-C15â:â0. The draft genome sequences revealed a DNA G+C content of 64.6 mol% for EXRC-4A-4T and 65.8 mol% for RC-2-3T. Based on this polyphasic study, EXRC-4A-4T and RC-2-3T represent two novel species within the genera Rhodococcus and Pseudarthrobacter, respectively. We propose the names Rhodococcus navarretei sp. nov. and Pseudarthrobacter quantipunctorum sp. nov. The type strains are Rhodococcus navarretei EXRC-4A-4T and Pseudarthrobacter quantipunctorum RC-2-3T. These strains have been deposited deposited in the CChRGM and BCCM/LMG culture collections with entry numbers RGM 3539/LMG 33621 and RGM 3538/LMG 33620, respectively.
Assuntos
Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Hibridização de Ácido Nucleico , Filogenia , RNA Ribossômico 16S , Rhodococcus , Análise de Sequência de DNA , Microbiologia do Solo , Rhodococcus/genética , Rhodococcus/classificação , Rhodococcus/isolamento & purificação , Rhodococcus/metabolismo , RNA Ribossômico 16S/genética , Regiões Antárticas , DNA Bacteriano/genética , Camada de Gelo/microbiologia , Actinomycetales/genética , Actinomycetales/isolamento & purificação , Actinomycetales/classificação , Actinomycetales/metabolismoRESUMO
BACKGROUND: Bacterial biosynthesis of fluorescent nanoparticles or quantum dots (QDs) has emerged as a unique mechanism for heavy metal tolerance. However, the physiological pathways governing the removal of QDs from bacterial cells remains elusive. This study investigates the role of minicells, previously identified as a means of eliminating damaged proteins and enhancing bacterial resistance to stress. Building on our prior work, which unveiled the formation of minicells during cadmium QDs biosynthesis in Escherichia coli, we hypothesize that minicells serve as a mechanism for the accumulation and detoxification of QDs in bacterial cells. RESULTS: Intracellular biosynthesis of CdS QDs was performed in E. coli mutants ΔminC and ΔminCDE, known for their minicell-producing capabilities. Fluorescence microscopy analysis demonstrated that the generated minicells exhibited fluorescence emission, indicative of QD loading. Transmission electron microscopy (TEM) confirmed the presence of nanoparticles in minicells, while energy dispersive spectroscopy (EDS) revealed the coexistence of cadmium and sulfur. Cadmium quantification through flame atomic absorption spectrometry (FAAS) demonstrated that minicells accumulated a higher cadmium content compared to rod cells. Moreover, fluorescence intensity analysis suggested that minicells accumulated a greater quantity of fluorescent nanoparticles, underscoring their efficacy in QD removal. Biosynthesis dynamics in minicell-producing strains indicated that biosynthesized QDs maintained high fluorescence intensity even during prolonged biosynthesis times, suggesting continuous QD clearance in minicells. CONCLUSIONS: These findings support a model wherein E. coli utilizes minicells for the accumulation and removal of nanoparticles, highlighting their physiological role in eliminating harmful elements and maintaining cellular fitness. Additionally, this biosynthesis system presents an opportunity for generating minicell-coated nanoparticles with enhanced biocompatibility for diverse applications.
Assuntos
Compostos de Cádmio , Nanopartículas , Pontos Quânticos , Sulfetos , Escherichia coli/metabolismo , Cádmio , Nanopartículas/química , Pontos Quânticos/química , Corantes/metabolismoRESUMO
Isolation of hydrocarbon-degrading bacteria is a key step for the study of microbiological diversity, metabolic pathways, and bioremediation. However current strategies lack simplicity and versatility. We developed an easy method for the screening and isolation of bacterial colonies capable of degrading hydrocarbons, such as diesel or polycyclic aromatic hydrocarbons (PAHs), as well as the pollutant explosive, 2,4,6-trinitrotoluene (TNT). The method uses a two-layer solid medium, with a layer of M9 medium, and a second layer containing the carbon source deposited through the evaporation of ethanol. Using this medium we grew hydrocarbon-degrading strains, as well as TNT-degrading isolates. We were able to isolate PAHs-degrading bacterial colonies directly from diesel-polluted soils. As a proof of concept, we used this method to isolate a phenanthrene-degrading bacteria, identified as Acinetobacter sp. and determined its ability to biodegrade this hydrocarbon.
Assuntos
Poluentes Ambientais , Hidrocarbonetos Policíclicos Aromáticos , Poluentes do Solo , Trinitrotolueno , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Trinitrotolueno/metabolismo , Bactérias , Biodegradação Ambiental , Poluentes Ambientais/metabolismo , Microbiologia do Solo , Poluentes do Solo/metabolismoRESUMO
Two motile, rod-shaped, Gram-stain-negative bacterial strains, TNT11T and TNT19T, were isolated from soil samples collected at Deception Island, Antarctica. According to the 16S rRNA gene sequence similarity, both strains belong to the genus Pseudomonas. Further genomic analyses based on ANI and dDDH suggested that these strains were new species. Growth of strain TNT11T is observed at 0-30 â (optimum, 20 â), pH 4.0-9.0 (optimum, pH 6.0) and in the presence of 0-5.0% NaCl (optimum, 1% NaCl), while for TNT19T is observed at 0-30 â (optimum between 15 and 20 â), pH 5.0-9.0 (optimum, pH 6.0) and in the presence of 0-5.0% NaCl (optimum between 0 and 1% NaCl). The fatty acid profile consists of the major compounds; C16:0 and C16:1 ω6 for TNT11T, and C16:0 and C12:0 for TNT19T. Based on the draft genome sequences, the DNA G + C content for TNT11T is 60.43 mol% and 58.60 mol% for TNT19T. Based on this polyphasic study, TNT11T and TNT19T represent two novel species of the genus Pseudomonas, for which the proposed names are Pseudomonas violetae sp. nov. and Pseudomonas emilianonis sp. nov., respectively. The type strains are Pseudomonas violetae TNT11T (= RGM 3443T = LMG 32959T) and Pseudomonas emilianonis TNT19T (= RGM 3442T = LMG 32960T). Strains TNT11T and TNT19T were deposited to CChRGM and BCCM/LMG with entry numbers RGM 3443/LMG 32959 and RGM 3442/LMG 32960, respectively.
Assuntos
Fosfolipídeos , Pseudomonas , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Regiões Antárticas , Pseudomonas/genética , Cloreto de Sódio , DNA Bacteriano/genética , Análise de Sequência de DNA , Hibridização de Ácido Nucleico , Filogenia , Técnicas de Tipagem Bacteriana , Ácidos Graxos/química , Enganação , SoloRESUMO
A Gram-stain-positive, catalase-positive, non-motile bacteria, with a rod-coccus cycle (designated as EH-1B-1T) was isolated from a soil sample from Union Glacier in Ellsworth Mountains, Antarctica. Strain EH-1B-1T had an optimal growth temperature of 28â°C and grew at pH 7-10. The major cellular fatty acids were anteiso-C15â:â0, iso-C15â:â0, C16â:â0 and anteiso-C17â:â0. The G+C content based on the whole genome sequence was 63.1âmol%. Strain EH-1B-1T was most closely related to members of the genus Arthrobacter, namely Arthrobacter subterraneus and Arthrobacter tumbae. The strain grew on tryptic soy agar, Reasoner's 2A agar, lysogeny broth agar and nutrient agar. The average nucleotide identity and digital DNA-DNA hybridization values between strain EH-1B-1T and its closest reference type strains ranged from 78 to 88â% and from 20.9 to 36.3â%, respectively. Based on phenotypic, chemotypic and genotypic evidence, it is proposed that strain EH-1B-1T represents a novel species of Arthrobacter, for which the name Arthrobacter vasquezii sp. nov. is proposed, with strain EH-1B-1T (RGM 3386T=LMG 32961T) as the type strain.