Enabling the next steps in cancer immunotherapy: from antibody-based bispecifics to multispecifics, with an evolving role for bioconjugation chemistry

In the last two decades, immunotherapy has established itself as one of the leading strategy for cancer treatment, as illustrated by the exponentially growing number of related clinical trials. This trend was, in part, prompted by the clinical success of both immune checkpoint modulation and immune cell engagement, to restore and/or stimulate the patient’s immune system’s ability to fight the disease. These strategies were sustained by progress in bispecific antibody production. However, despite the decisive progress made in the treatment of cancer, toxicity and resistance are still observed in some cases. In this review, we intitally provide an overview of the monoclonal and bispecific antibodies developed with the objective to restore immune system functions to treat cancer (cancer immunotherapy), either being through immune checkpoint modulation, immune cell engagement or a combination of both. Their production, design strategy and impact on the clinical trial landscape were also addressed. In the second part, the concept of multispecific antibody formats, notably MuTICEMs (Multispecific Targeted Immune Cell Engager & Modulator), as a possible answer to current immunotherapy limitations is investigated. We believe it could be the next step to take for the cancer immunotherapy research and expose why bioconjugation chemistry might play a key role in these future developments

Nutrigenomics 2.0: The Need for Ongoing and Independent Evaluation and Synthesis of Commercial Nutrigenomics Tests' Scientific Knowledge Base for Responsible Innovation

Nutrigenomics is an important strand of precision medicine that examines the bidirectional interactions of the genome and nutritional exposures, and attendant health and disease outcomes. This perspectives article presents the new concept of "Nutrigenomics 2.0," so as to cultivate and catalyze the next generation research and funding priorities for responsible and sustainable knowledge-based innovations. We further contextualize our recent study of the 38 genes included in commercially available nutrigenomics tests, and offer additional context in relation to the 2014 American Academy of Nutrition and Dietetics position. Finally, we make a call in the best interest of the nutrigenomics science community, governments, global society, and commercial nutrigenomics test providers that new evidence evaluation and synthesis platforms are created concerning nutrigenomics tests before they become commercially available. The proposed assessment and synthesis of nutrigenomics data should be carried out on an ongoing dynamic basis with periodic intervals and/or when there is a specific demand for evidence synthesis, and importantly, in ways that are transparent where conflict of interests are disclosed fully by the involved parties, be they scientists, industry, governments, citizens, social scientists, or ethicists. We submit that this will cultivate responsible innovation, and business models that are sustainable, robust, and stand the test of time and context

A novel thiol-labile cysteine protecting group for peptide synthesis based on a pyridazinedione (PD) scaffold

Herein we report a thiol-labile cysteine protecting group based on an unsaturated pyridazinedione (PD) scaffold. We establish compatibility of the PD in conventional solid phase peptide synthesis (SPPS), showcasing this in the on-resin synthesis of biologically relevant oxytocin. Furthermore, we establish the applicability of the PD protecting group towards both microwave-assisted SPPS and native chemical ligation (NCL) in a model system

Long Span DNA Paired-End-Tag (DNA-PET) Sequencing Strategy for the Interrogation of Genomic Structural Mutations and Fusion-Point-Guided Reconstruction of Amplicons

10.1371/journal.pone.0046152PLoS ONE79

Simplicity in Visual Representation: A Semiotic Approach

Simplicity, as an ideal in the design of visual representations, has not received systematic attention. High-level guidelines are too general, and low-level guidelines too ad hoc, too numerous, and too often incompatible, to serve in a particular design situation. This paper reviews notions of visual simplicity in the literature within the analytical framework provided by Charles Morris' communication model, specifically, his trichotomy of communication levels—the syntactic, the semantic, and the pragmatic. Simplicity is ultimate ly shown to entail the adjudication of incompatibilities both within, and between, levels.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68281/2/10.1177_105065198700100103.pd

Landscape, Memory, and the Shifting Regional Geographies of Northwest Bosnia-Herzegovina

Writing and arguing with older discourses that have informed the subdiscipline of regional geography and setting them against new ways of conceiving of the region, this article considers the northwest of Bosnia-Herzegovina as a site that calls for a newly animated form of regional study. Of particular concern here is the role that memory and commemorative practices play in such a spatial schema. The monumental landscapes of the Tito regime and its collective commemoration of World War II sit alongside and are troubled by the more recent traumas and spaces of unmarked death associated with the ethnic war in Bosnia during the early 1990s. Read together, northwest Bosnia-Herzegovina functions as a vivid exemplar for understanding traumatic historical mourning as a phenomenological process that is inseparable from the wider geopolitical landscape