Search

Aberrant activation of the Wnt signalling pathway is required for tumour initiation and survival in the majority of colorectal cancers. The development of inhibitors of Wnt signalling has been the focus of multiple drug discovery programs targeting colorectal cancer and other malignancies associated with aberrant pathway activation. However, progression of new clinical entities targeting the Wnt pathway has been slow. One challenge lies with the limited predictive power of 2D cancer cell lines because they fail to fully recapitulate intratumoural phenotypic heterogeneity. In particular, the relationship between 2D cancer cell biology and cancer stem cell function is poorly understood. By contrast, 3D tumour organoids provide a platform in which complex cell-cell interactions can be studied. However, complex 3D models provide a challenging platform for the quantitative analysis of drug responses of therapies that have differential effects on tumour cell subpopulations. Here, we generated tumour organoids from colorectal cancer patients and tested their responses to inhibitors of Tankyrase (TNKSi) which are known to modulate Wnt signalling. Using compounds with 3 orders of magnitude difference in cellular mechanistic potency together with image-based assays, we demonstrate that morphometric analyses can capture subtle alterations in organoid responses to Wnt inhibitors that are consistent with activity against a cancer stem cell subpopulation. Overall our study highlights the value of phenotypic readouts as a quantitative method to asses drug-induced effects in a relevant preclinical model.

Background: Immunization is considered the most effective strategy for infectious disease control and maintaining global health. Conventional vaccines have successfully targeted a broad spectrum of pathogens. However, a large number of untargeted diseases still remain. Introduction of novel Genetically Modified (GM) vaccines allow development of new improved vaccines and immunotherapeutics. Moreover, GM vaccines can also target non-communicable diseases outside the range of infectious diseases, including cancer, autoimmune diseases, and allergies. Methods: We compiled novel and unique datasets encompassing data from literature, patent documents, clinical trials, and vaccine registers in order to provide a thorough overview of the GM market.Results: Based on patent data, we found that most patent applications were filed in North America, Asia, and Europe, which coincides with the locations of the largest companies and institutes. Looking at clinical trial data we forecast marketing of two next generation GM vaccines, targeting cancer and malaria. In addition, we calculated phase transition success rates of 82% (phase 1-2) and 76% (phase 2-3).Conclusions: These findings indicate viable regions for GM vaccine research and development. Phase transition success rates of 82% (phase 1-2) and 76% (phase 2-3) predict a relatively high chance of marketing approval. Increased registrations of GM vaccines complemented by rising numbers of patent applications suggest global growth of the GM vaccine market, which currently holds a proportion of nearly 20% of the total vaccine market.

A quantitative method is presented to rank strengths, weaknesses, opportunities, and threats (SWOT) of modified vaccinia virus Ankara (MVA) as a platform for pre-pandemic and pandemic influenza vaccines. Analytic hierarchy process (AHP) was applied to achieve pairwise comparisons among SWOT factors in order to prioritize them. Key opinion leaders (KOLs) in the influenza vaccine field were interviewed to collect a unique dataset to evaluate the market potential of this platform. The purpose of this study, to evaluate commercial potential of the MVA platform for the development of novel generation pandemic influenza vaccines, is accomplished by using a SWOT and AHP combined analytic method. Application of the SWOT AHP model indicates that its strengths are considered more important by KOLs than its weaknesses, opportunities, and threats. Particularly, the inherent immunogenicity capability of MVA without the requirement of an adjuvant is the most important factor to increase commercial attractiveness of this platform. Concerns regarding vector vaccines and anti-vector immunity are considered its most important weakness, which might lower public health value of this.platform. Furthermore, evaluation of the results of this study emphasizes equally important role that threats and opportunities of this platform play. This study further highlights unmet needs in the influenza vaccine market, which could be addressed by the implementation of the MVA platform. Broad use of MVA in clinical trials shows great promise for this vector as vaccine platform for pre-pandemic and pandemic influenza and threats by other respiratory viruses. Moreover, from the results of the clinical trials seem that MVA is particularly attractive for development of vaccines against pathogens for which no, or only insufficiently effective vaccines, are available. (C) 2015 The Authors. Published by Elsevier Ltd.

The global vaccine market is diverse while facing a plethora of novel developments. Genetic modification (GM) techniques facilitate the design of 'smarter' vaccines. For many of the major infectious diseases of humans, like AIDS and malaria, but also for most human neoplastic disorders, still no vaccines are available. It may be speculated that novel GM technologies will significantly contribute to their development. While a promising number of studies is conducted on GM vaccines and GM vaccine technologies, the contribution of GM technology to newly introduced vaccines on the market is disappointingly limited. In this study, the field of vector-based GM vaccines is explored. Data on currently available, actually applied, and newly developed vectors is retrieved from various sources, synthesised and analysed, in order to provide an overview on the use of vector-based technology in the field of GM vaccine development. While still there are only two vector-based vaccines on the human vaccine market, there is ample activity in the fields of patenting, preclinical research, and different stages of clinical research. Results of this study revealed that vector-based vaccines comprise a significant part of all GM vaccines in the pipeline. This study further highlights that poxviruses and adenoviruses are among the most prominent vectors in GM vaccine development. After the approval of the first vectored human vaccine, based on a flavivirus vector, vaccine vector technology, especially based on poxviruses and adenoviruses, holds great promise for future vaccine development. It may lead to cheaper methods for the production of safe vaccines against diseases for which no or less perfect vaccines exist today, thus catering for an unmet medical need. After the introduction of Jenner's vaccinia virus as the first vaccine more than two centuries ago, which eventually led to the recent eradication of smallpox, this and other viruses may now be the basis for constructing vectors that may help us control other major scourges of mankind.

On the 9th of November 2015, preceding the World Veterinary Vaccine Congress, a workshop was held to discuss how veterinary vaccines can be deployed more rapidly to appropriately respond to future epizootics in Europe. Considering their potential and unprecedented suitability for surge production, the workshop focussed on vaccines based on genetically engineered viruses and replicon particles. The workshop was attended by academics and representatives from leading pharmaceutical companies, regulatory experts, the European Medicines Agency and the European Commission. We here outline the present regulatory pathways for genetically engineered vaccines in Europe and describe the incentive for the organization of the pre-congress workshop. The participants agreed that existing European regulations on the deliberate release of genetically engineered vaccines into the environment should be updated to facilitate quick deployment of these vaccines in emergency situations.

This study provides a quantitative multidisciplinary approach to identify and prioritize the main implementation challenges of the MVA platform for novel influenza vaccines using a tailor-made prioritization process. Influential key opinion leaders (KOL’s) in the field of vaccine research, development, and manufacturing were approached to participate in this study. Semi-structured interviews were performed with 32 KOL’s representing the regulatory, industry, and academia fields. The opinions were analyzed quantitatively, through various ranking methods that were integrated and adapted to fit the purpose of this study, identifying 6 implementation challenges main categories, 21 implementation challenges categories, and 39 implementation challenges underlying causes. The most significant barriers are associated with “production & speed” category whereas the least significant are associated with “regulatory” category. Perspectives among the KOL’s proved to be divergent with regard to implementation challenges for the MVA platform. Through comparing these perspectives, useful information on current and potential future implementation challenges of novel platforms in general may be expected. Providing an overview and assessment to reveal these challenges may lead to a more substantial situation for all stakeholders involved, given that such an overview allows for the recognition of various implementation challenges from a multidisciplinary perspective, making it possible to identify underlying causes that contribute to the successful implementation of the MVA platform. Remarkably, analysis of implementation challenges resulted in core challenges that resemble similarities between the three perspectives.

At present, industries within the health and life science sector are moving towards one another resulting in new industries such as the medical nutrition industry. Medical nutrition products are specific nutritional compositions for intervention in disease progression and symptom alleviation. Industry convergence, described as the blurring of boundaries between industries, plays a crucial role in the shaping of new markets and industries. Assuming that the medical nutrition industry has emerged from the convergence between the food and pharma industries, it is crucial to research how and which distinct industry domains have contributed to establish this relatively new industry. The first two stages of industry convergence (knowledge diffusion and consolidation) are measured by means of patent analysis. First, the extent of knowledge diffusion within the medical nutrition industry is graphed in a patent citation interrelations network. Subsequently the consolidation based on technological convergence is determined by means of patent co-classification. Furthermore, the medical nutrition core domain and technology interrelations are measured by means of a cross impact analysis. This study proves that the medical nutrition industry is a result of food and pharma convergence. It is therefore crucial for medical nutrition companies to effectively monitor technological developments within as well as across industry boundaries. This study further reveals that although the medical nutrition industry's core technology domain is food, technological development is mainly driven by pharmaceutical/pharmacological technologies Additionally, the results indicate that the industry has surpassed the knowledge diffusion stage of convergence, and is currently in the consolidation phase of industry convergence. Nevertheless, while the medical nutrition can be classified as an industry in an advanced phase of convergence, one cannot predict that the pharma and food industry segments will completely converge or whether the medical industry will become an individual successful industry. © 2013 Weenen et al.