A multi-peptide, dual-adjuvant telomerase vaccine (GX301) is highly immunogenic in patients with prostate and renal cancer

Background

Anti-tumor vaccination is a new frontier in cancer treatment applicable to immunogenic neoplasms such as prostate and renal cancers. GX301 is a vaccine constituted by four telomerase peptides and two adjuvants, Montanide ISA-51 and Imiquimod.

Objective

The aim of this study was to analyze safety and tolerability of GX301 in an open-label, phase I/II trial. Immunological and clinical responses were also evaluated as secondary endpoints.

Experimental design

GX301 was administered by intradermally injecting 500 μg of each peptide (dissolved in Montanide ISA-51) in the skin of the abdomen. Imiquimod was applied as a cream at the injection sites. The protocol included 8 administrations at days 1, 3, 5, 7, 14, 21, 35, 63. Eligible patients were affected with stage IV prostate or renal cancer resistant to conventional treatments. Patients were clinically and immunologically monitored up to 6 months from the first immunization.

Results

No grade 3–4 adverse events were observed. Evidence of vaccine-specific immunological responses was detected in 100 % of patients. Disease stabilization occurred in 4 patients. Prolonged progression-free survival and overall survival were observed in patients showing a full pattern of vaccine-specific immunological responses.

Conclusion

GX301 demonstrated to be safe and highly immunogenic. Further studies are needed to determine its clinical efficacy.     

Product social impact assessment

Purpose

Whereas the business evolution of environmental sustainability metrics has advanced significantly over the past decade, social sustainability at product level is still relatively immature. Research continues to support the front runners on organisational sustainability, while workable solutions at product level have not yet been addressed sufficiently. Triggered by this imbalance, a group of experts from large companies decided to join forces, initiating the Roundtable for Product Social Metrics.

Methods

Starting in early 2013, this group of companies aimed to (i) consolidate principles for product social sustainability assessment and harmonise approaches, (ii) align with other global initiatives and share with other companies and (iii) develop solutions for cross-cutting implementation issues. In order to be able to produce a comprehensive method for social impact assessment that provides enough flexibility for individual requirements, the Roundtable developed a method based on the approaches of the participant companies and external references such as the UNEP/SETAC Guidelines for Social Life-Cycle Assessment of Products and corporate level standards. Guiding principles were defined for the development of the method.

Results and discussion

The results of the first two phases of the Roundtable for Product Social Metrics are documented in a handbook, which proposes a practical method for organisations to assess the social impacts of a product or a service along its life cycle. The handbook outlines an aligned method for social impact assessment at a product level offering two approaches: quantitative and scale based. The method was developed to allow reasoned assessment of overall performance by including social topics and performance indicators that reflect positive and negative impacts of the product on three stakeholder groups: workers, consumers and local communities. Nineteen social topics are proposed, together with their individual performance indicators, including detailed definitions. Application examples and recommendations for the communication of results are also included in the handbook.

Conclusions

The method can be applied in numerous scenarios, from understanding improvement opportunities and steering product development in different stages, to providing support for decision making and external communications. However, the method still has further potential for improvement, inter alia that the proposed indicators are not fully applicable to small farmers, SMEs and the self-employed, as well as that the indicators are mainly at inventory level. Furthermore, the proposed method is strongly dependent on the availability of data.

     

Towards social life cycle assessment: a quantitative product social impact assessment

Purpose

The main goal of this paper is to present the feasibility of the quantitative method presented in the Product Social Impact Assessment (PSIA) handbook throughout a case study. The case study was developed to assess the social impacts of a tire throughout its entire life cycle. We carried out this case study in the context of the Roundtable for the Product Social Metrics project in which 13 companies develop two methodologies, a qualitative and a quantitative one, for assessing the social impact of product life cycle.

Methods

The quantitative methodology implemented for assessing the social impact of a Run On Flat tire mounted in a BMW 3 series consists of 26 indicators split in three groups. Each group represents a stakeholder group. Primary data of the quantitative indicators were collected along the product life cycle of the Run On Flat by involving the companies, which owned the main steps of the product life cycle. Throughout this case study, an ideal/worst-case scenario was defined for the distance-to-target approach to compare the social performances of more products when they are available.

Results and discussion

The implementation of the PSIA quantitative method to a Run On Flat illustrated the necessity to have a referencing step in order to interpret the results. This is particularly important when the results are used to support decision-making process in which no experts are involved. It frequently happens in a big company where the management level has to take often decisions on different topics. Reference values were defined using ideal or worst-case-target scenarios (Fontes et al. 2014). For those topics where it was possible, an ideal/ethical scenario was defined, e.g., 0 h of child labor per product. In other cases, we defined a worst-case scenario, e.g., 0 training hours per product. It was then possible to interpret the results using a distance-to-target approach. A matrix was developed in the case study for identifying in which step of the product life cycle data is not available; that means we need more transparency in the supply chain.

Conclusions

Each value of the matrix can be compared to the ideal/worst scenario to compare the step to each other and to identify along the product life cycle which step and the relative supplier that needs further measures to improve the product performance. Furthermore, a quantitative value for each indicator related to the product life cycle is calculated and compared with the ideal/worst scenario. The case study on Run On Flat represents the first implementation of the quantitative method of PSIA.

     

An Italian tomato “Cuore di Bue” case study: challenges and benefits using subcategory assessment method for social life cycle assessment

Purpose

The main purpose of this study is to present an implementation of the subcategory assessment method (SAM) to the life cycle of an Italian variety of tomato called “Cuore di Bue” produced by an Italian cooperative. The case study was used to use the methodology proposed in compliance with the guidelines of social life cycle assessment (S-LCA) in order to highlight issues for the improvement of SAM. A summary of strengths and weaknesses of the methodology as well as the social performance of the considered Italian tomato is an important result of this case study.

Methods

The methodology used is based on SAM. The UNEP/SETAC guidelines of S-LCA and the complementary methodological sheets were used as main references to carry out SAM, and it was used to assess the social performances of Cuore di Bue. The focus was on the assessment of the following three out of five stakeholder groups presented in the guidelines: workers, local community and consumers. Specific questionnaires have been developed to collect the inventory data related to each stakeholder group and along the product life cycle.

Results and discussion

SAM of Cuore di Bue showed a range of values, between 2 and 3 (C-B) for consumer stakeholder group and mainly 3 (B) for the local community and worker stakeholders. Because the best performance (A) is related to a numerical value of 4, better performances were not identified, owing to no propagation of actions in the value chain. The collective bargaining, transparency, feedback mechanism and privacy are the subcategories with the worst performance, but at the same time with more potential for improvements.

Conclusions

The implementation of SAM on Cuore di Bue allowed us to demonstrate how SAM transforms qualitative data into semi-quantitative information through a score scale that can help a decision maker achieve a product overview. SAM has been implemented on Cuore di Bue; the product assessment, the strengths and weaknesses of the methodology are identified and discussed as well. It has been possible to present the best and worst performances in product life cycle, by identifying the phase or the subcategories with good or bad performance. However, in this case study, as the same company owns most of the product life cycle taken into account, the majority of social performances are identical, and this may represent a limit of the methodology or that more organisations along the life cycle must be taken into account (for example, energy, distribution).

     

Opposite effects of bFGF and TGF-beta on collagen metabolism by human periodontal ligament fibroblasts

This study evaluated the effects of bFGF and TGF-beta, individually and combined, on cell proliferation and collagen metabolism. Primary human periodontal ligament cells were stimulated with two concentrations (1 and 10 ng/ml) of each growth factor, both individually and combined. Proliferation was determined by a commercial biochemical assay. Real time RT-PCR determined gene expression of MMP-1 and -2, collagen types I and III, TIMP-1, -2 and -3. Autocrine effects on synthesis of bFGF and TGF-beta were evaluated by ELISA. Only TGF-beta, either isolated or associated with bFGF, significantly increased cell proliferation. TGF-beta had anabolic effects, increasing expression of type I and III collagen as well as of TIMPs, whereas bFGF had opposite effects. When bFGF and TGF-beta were associated, the anabolic effects prevailed. Synthesis of TGF-beta was induced only by the association of lower concentrations of the growth factors, whereas there was a dose-dependent production of bFGF. It is concluded that bFGF had a predominantly catabolic effect, and TGF-beta exerted an anabolic effect on hPDL cells.     

Lipocortin IV is a basolateral cytoskeleton constituent of rabbit enterocytes.

A monoclonal antibody, BL7B1, which specifically recognized rabbit lipocortin IV, was produced. The BL7B1 epitope is localized between the methionine residues that occupy positions 148 and 259 in human lipocortin IV. Immunofluorescence and subcellular fractionation studies showed that in the rabbit enterocytes, lipocortin IV is specifically associated with the basolateral membranes. When these membranes are solubilized by Triton X-100 in the presence of 1 mM of Ca2+ the lipocortin IV, like the cytoskeleton, remained insoluble suggesting that it might be associated with this structure in vivo. No lipocortin IV was detected in the brush border using immunofluorescence techniques and less than 10% of the amount present in the purified basolateral membranes was detected in the brush border membrane fraction.     

Neuronal growth and the Steiner problem.

In this paper we conjecture that neuronal networks develop following an optimality principle. We point out that a neuronal outgrowth in culture may be seen as the solution of a classical optimization problem: the "Steiner Problem". A neuron might grow minimizing a "cost", which may be determined by the viscoelastic properties of the neuron cytoplasm. We then discuss the role of chemiotactic factors such as the Nerve Growth Factor (NGF) in an optimized neuronal development in vivo. Finally we suggest, with some mathematical arguments, that the optimization of the elastic forces in the growing neuron may give rise to a "fractal" structure.     

High expression levels of the "erythroid/brain" type glucose transporter (GLUT1) in the basal cells of human eye conjunctiva and oral mucosa reconstituted in culture

The expression of the "erythroid/brain" type glucose transporter (GLUT1) seems to be a feature of "barrier" tissues, at least in humans. Recently, we reported that GLUT1 is highly expressed in the basal layers of either "authentic" human epidermis or human epidermis reconstituted in culture and that its expression seems to be related to keratinocyte differentiation. In this paper we demonstrate that GLUT1 is selectively expressed in the basal layers of either eye conjunctiva epithelia or oral mucosa, reconstituted in culture starting from 1-2 mm2 bioptic specimens of normal human tissue. GLUT1 mRNA and protein levels are very high in conjunctiva and oral mucosa, 2-3 times higher than in epidermis reconstituted in culture. Taking into account its localization at the border of tissues not directly vascularized, but metabolically active, GLUT1 could play an important role in controlling the entry of glucose into these firmly guarded tissues.