Evaluating the Cellular Targets of Anti-4-1BB Agonist Antibody during Immunotherapy of a Pre-Established Tumor in Mice

Manipulation of the immune system represents a promising avenue for cancer therapy. Rational advances in immunotherapy of cancer will require an understanding of the precise correlates of protection. Agonistic antibodies against the tumor necrosis factor receptor family member 4-1BB are emerging as a promising tool in cancer therapy, with evidence that these antibodies expand both T cells as well as innate immune cells. Depletion studies have suggested that several cell types can play a role in these immunotherapeutic regimens, but do not reveal which cells must directly receive the 4-1BB signals for effective therapy.We show that re-activated memory T cells are superior to resting memory T cells in control of an 8-day pre-established E.G7 tumor in mice. We find that ex vivo activation of the memory T cells allows the activated effectors to continue to divide and enter the tumor, regardless of antigen-specificity; however, only antigen-specific reactivated memory T cells show any efficacy in tumor control. When agonistic anti-4-1BB antibody is combined with this optimized adoptive T cell therapy, 80% of mice survive and are fully protected from tumor rechallenge. Using 4-1BB-deficient mice and mixed bone marrow chimeras, we find that it is sufficient to have 4-1BB only on the endogenous host alphabeta T cells or only on the transferred T cells for the effects of anti-4-1BB to be realized. Conversely, although multiple immune cell types express 4-1BB and both T cells and APC expand during anti-4-1BB therapy, 4-1BB on cells other than alphabeta T cells is neither necessary nor sufficient for the effect of anti-4-1BB in this adoptive immunotherapy model.This study establishes alphabeta T cells rather than innate immune cells as the critical target in anti-4-1BB therapy of a pre-established tumor. The study also demonstrates that ex vivo activation of memory T cells prior to infusion allows antigen-specific tumor control without the need for reactivation of the memory T cells in the tumor

Monitoring system with multimodal sensor for electrical conductivity and hydrogen-ion concentration of causative agents of underarm odor

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Influence of carbohydrates on the isolation of lactic acid bacteria

Aims: To determine the influence of carbohydrates on enrichment isolation of lactic acid bacteria from different niches. Methods and Results: Lactic acid bacteria in three traditional fermented products in southern Africa (amasi, mahewu and tshwala) and in three fresh samples (two flowers and a fruit) were enrichment cultured in media supplemented with 13 different carbohydrates. Diversity of lactic acid bacteria was determined by PCR-denaturing-gradient gel electrophoresis. Carbohydrates used in enrichment media had a big impact on the isolation of lactic acid bacteria from fermented products. Depending on the carbohydrates tested, the number of species detected ranged from one to four in amasi, one to five in mahewu and one to three in tshwala. Fructose and mannitol selected for relatively higher numbers of lactic acid bacteria in fermented products. Specific relationships between substrates and lactic acid bacteria have been noted. On the other hand, small influences were found among carbohydrates tested in flowers and fruit. Conclusion: Carbohydrates have a big impact on the isolation of a variety of lactic acid bacteria in fermented food. Significance and Impact of the Study: This is the first study that reports the influence of carbohydrates on the enrichment of lactic acid bacteria. © 2011 The Authors. Journal of Applied Microbiology © 2011 The Society for Applied Microbiology.Articl

Bifidobacterium reuteri sp. nov., Bifidobacterium callitrichos sp. nov., Bifidobacterium saguini sp. nov., Bifidobacterium stellenboschense sp. nov. and Bifidobacterium biavatii sp. nov. isolated from faeces of common marmoset (Callithrix jacchus) and red-handed tamarin (Saguinus midas)

Five strains of bifidobacteria were isolated from faeces of a common marmoset (Callithrix jacchus) and a red-handed tamarin (Saguinus midas). The five isolates clustered inside the phylogenetic group of the genus Bifidobacterium but did not show high sequence similarities between the isolates and to known species in the genus by phylogenetic analysis based on 16S rRNA gene sequences. Sequence analyses of dnaJ1 and hsp60 also indicated their independent phylogenetic positions to each other in the Bifidobacterium cluster. DNA G+C contents of the species ranged from 57.3 to 66.3mol%, which is within the values recorded for Bifidobacterium species. All isolates showed fructose-6-phosphate phosphoketolase activity. Based on the data provided, the five isolates represent five novel species, for which the names Bifidobacterium reuteri sp. nov. (type strain: AFB22-1 T=JCM 17295 T=DSM 23975 T), Bifidobacterium callitrichos sp. nov. (type strain: AFB22-5 T=JCM 17296 T=DSM 23973 T), Bifidobacterium saguini sp. nov. (type strain: AFB23-1 T=JCM 17297 T=DSM 23967 T), Bifidobacterium stellenboschense sp. nov. (type strain: AFB23-3 T=JCM 17298 T=DSM 23968 T) and Bifidobacterium biavatii sp. nov. (type strain: AFB23-4 T=JCM 17299 T=DSM 23969 T) are proposed. © 2011 Elsevier GmbH

Functional properties of linseed meal fractions: Application as nutraceutical ingredient

Brown linseed (Linum ustatissimum) is pressed to produce oil, and the remaining linseed meal is rich in protein and soluble dietary fiber. To utilize the derivatives of linseed meal as food ingredients or additives, linseed meal was fractionated by controlling pH on a pilot-plant scale. Chemical composition, functional properties and health-related bioactivities, such as angiotensin-converting enzyme (ACE) inhibition and antioxidant activities, of the fractions were then analyzed. The alkaline soluble protein had the highest content of secoisolariciresinol diglucoside (SDG) and showed good emulsification activity, comparable to that of whole egg. The acid-soluble fraction showed the highest viscosity. ACE inhibition, antioxidant activities, and bile acid binding activity were observed in the soluble dietary fiber fraction. There was no correlation between SDG content and bioactivities. These findings indicate that the acid-soluble fraction is useful as a food ingredient to increase viscosity, while the soluble dietary fiber fraction has health-related features

Characterization and emended description of lactobacillus kunkeei as a fructophilic lactic acid bacterium

Lactobacillus kunkeei is an inhabitant of fructose-rich niches and is a potential member of the fructophilic lactic acid bacteria. In the present study, the phylogenetic and biochemical characteristics of the type strain and eight isolates of L. kunkeei, originating from wine, flowers and honey, were studied. The nine isolates, including the type strain, formed a well-defined phylogenetic subcluster based on the analysis of 16S rRNA gene sequences. The subcluster was not closely related to other subclusters in the Lactobacillus phylogenetic group. Biochemically, the eight new isolates showed typical fructophilic characteristics. The eight isolates grew poorly on glucose, but grew well on fructose. Good growth on glucose was only recorded in the presence of electron acceptors. The type strain of L. kunkeei differed from the other isolates only on the basis of poor growth on fructose. Although they belong to a group of obligately heterofermentative lactic acid bacteria, all nine isolates, including the type strain, produced almost equimolar amounts of lactic acid and acetic acid and very little ethanol from glucose. Eight of the isolates can thus be regarded as typical 'obligately' fructophilic lactic acid bacteria. Although the type strain of L. kunkeei was phenotypically slightly different from the other isolates, it possessed several important fructophilic characteristics. On the basis of the evidence gathered in this study, the type strain of L. kunkeei is recognized as a member of the 'obligately' fructophilic lactic acid bacteria. © 2012 IUMS

Fructobacillus tropaeoli sp. nov., a fructophilic lactic acid bacterium isolated from a flower

A fructophilic lactic acid bacterium, designated strain F214-1T, was isolated from a flower of Tropaeolum majus in South Africa. Based on phylogenetic analysis of 16S rRNA gene sequences, the strain formed a subcluster with Fructobacillus ficulneus and Fructobacillus pseudoficulneus and, based on recA gene sequences, the strain formed a subcluster with F. ficulneus. DNA-DNA hybridization studies showed that strain F214-1T was phylogenetically distinct from its closest relatives. Acid was produced from the fermentation of D-glucose, D-fructose and D-mannitol only. D-Fructose was the preferred sole carbon and energy source and was fermented more rapidly than D-glucose. Growth of the strain on D-glucose under anaerobic conditions was very weak but external electron acceptors such as oxygen and pyruvate enhanced growth on D-glucose. Lactic acid and acetic acid were produced from D-glucose in equimolar amounts. Ethanol was produced at very low levels, despite the strain's obligately heterofermentative metabolism. Based on these data, strain F214-1T represents a novel species of fructophilic bacteria in the genus Fructobacillus, for which the name Fructobacillus tropaeoli sp. nov. is proposed. The type strain is F214-1T (=5JCM 16675T =DSM 23246T). © 2011 IUMS.Articl

Characterization and emended description of <I>Lactobacillus kunkeei </I>as a fructophilic lactic acid bacterium.

AgriwetenskappeInstituut Vir WynbiotegnologiePlease help us populate SUNScholar with the post print version of this article. It can be e-mailed to: [email protected]