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1.
Nanomedicine ; 37: 102443, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34303839

RESUMO

Neoantigen-based personalized vaccination has emerged as a viable method for tumor immunotherapy. Here we set up a DNA-based neoantigen vaccine platform with comprehensive identification of individual somatic mutations using whole-exome sequencing (WES) and RNA-seq, bioinformatic prediction of neo-epitopes, dendritic cell (DC)-based efficacy prevalidation of vaccine candidates, optimization of the DNA vaccine and its nanocarrier and adjuvant, and preparation of a liposome-encapsulated multiepitope DNA vaccine. The DNA vaccine was efficiently uptaken by DCs and induced effective immune response against mouse melanoma cells, leading to significant inhibition of melanoma tumor growth and reduction of lung metastasis in a mouse model. Numerous intratumoral infiltrated CD8+ T-cells with specific in vitro killing ability towards melanoma cells were identified. Our study offers evidence that a multiepitope neoantigen DNA vaccine in a nanocarrier can be exploited for personalized tumor immunotherapy and as a reliable prevalidation approach for rapid enrichment of effective neoantigens.


Assuntos
Vacinas Anticâncer/farmacologia , Imunoterapia , Melanoma/terapia , Medicina de Precisão , Vacinas de DNA/farmacologia , Animais , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Epitopos/genética , Epitopos/imunologia , Humanos , Lipossomos/química , Lipossomos/farmacologia , Melanoma/imunologia , Melanoma/patologia , Camundongos , Mutação/genética , Nanopartículas/química , Vacinas de DNA/genética , Vacinas de DNA/imunologia , Sequenciamento do Exoma
2.
Biotechnol Prog ; 28(4): 962-72, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22508691

RESUMO

The traditional distillation method for recovery of butanol from fermentation broth is an energy-intensive process. Separation of butanol based on adsorption methodology has advantages in terms of biocompatibility and stability, as well as economy, and therefore gains much attention. However, the application of the commercial adsorbents in the integrated acetone-butanol-ethanol (ABE) fermentation process is restricted due to the low recovery (less than 85%) and the weak capability of enrichment in the eluent (3-4 times). In this study, we investigated the sorption properties of butanol onto three kinds of adsorbents with different polarities developed in our laboratory, that is, XD-41, H-511, and KA-I resin. The sorption behaviors of single component and ABE ternary mixtures presented in the fermentation broths on KA-I resin were investigated. KA-I resin had higher affinity for butanol than for acetone, ethanol, glucose, acetic acid, and butyric acid. Multicomponent ABE sorption on KA-I resin was modeled using a single site extended Langmuir isotherm model. In a desorption study, all the adsorbed components were desorbed in one bed volume of methanol, and the recovery of butanol from KA-I resin was 99.7%. The concentration of butanol in the eluent was increased by a factor of 6.13. In addition, KA-I resin was successfully regenerated by two bed volumes of water. Because of its quick sorption, high sorption capacity, low cost, and ease of desorption and regeneration, KA-I resin exhibits good potential for compatibility with future ABE fermentation coupled with in situ recovery product removal techniques.


Assuntos
Acetona/isolamento & purificação , Butanóis/isolamento & purificação , Cromatografia/métodos , Clostridium acetobutylicum/metabolismo , Etanol/isolamento & purificação , Resinas Sintéticas/química , Acetona/metabolismo , Adsorção , Biocombustíveis/análise , Reatores Biológicos , Butanóis/metabolismo , Cromatografia/instrumentação , Meios de Cultura/química , Meios de Cultura/metabolismo , Etanol/metabolismo , Fermentação , Porosidade
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