Re-usable thermally reversible crosslinked adhesives from robust polyester and poly(ester urethane) Diels–Alder networks

The sustainable design of polymers for applications requires careful consideration of how they can be re-used or recycled at the end of service life. There has been considerable interest in covalent adaptable networks (CANs) which offer the potential of the properties of crosslinked polymers but where the materials can be reprocessed like thermoplastics. Although there have been advances in CAN chemistry, materials tend to creep and industrial applications are limited. Here we show thermally reversible crosslinked adhesives from dissociative Diels–Alder networks which can be re-used repeatedly with versatile adhesion and creep resistance. Monomer and isocyanate-free polyester and poly(ester urethane) prepolymers were successfully synthesized by facile techniques with high atom efficiency and the resulting CANs are easy to apply in bulk from the melt. Mechanical properties can be tuned depending on the prepolymer design with the networks providing versatile adhesion to different substrates and creep resistance to 70–80 °C, above both the Tg and Tm of the networks. The adhesives are thermally stable during application and can be re-used repeatedly by simple heating/cooling cycles in bulk, without solvents or additional process steps, providing the same level of performance. Our results demonstrate that these Diels–Alder networks are robust in mechanical performance up to the temperature where significant dissociation begins to occur. This opens the possibility for the considered design of prepolymer architecture and reversible chemistry to meet the performance requirements of different applications in a truly sustainable fashion via scalable, efficient, industrially facile methodologies – where materials are free of solvents or monomers in their synthesis, processing, application and re-use

Avelumab maintenance in advanced urothelial carcinoma: biomarker analysis of the phase 3 JAVELIN Bladder 100 trial

In a recent phase 3 randomized trial of 700 patients with advanced urothelial cancer (JAVELIN Bladder 100; NCT02603432), avelumab/best supportive care (BSC) significantly prolonged overall survival relative to BSC alone as maintenance therapy after first-line chemotherapy. Exploratory biomarker analyses were performed to identify biological pathways that might affect survival benefit. Tumor molecular profiling by immunohistochemistry, whole-exome sequencing and whole-transcriptome sequencing revealed that avelumab survival benefit was positively associated with PD-L1 expression by tumor cells, tumor mutational burden, APOBEC mutation signatures, expression of genes underlying innate and adaptive immune activity and the number of alleles encoding high-affinity variants of activating Fc gamma receptors. Pathways connected to tissue growth and angiogenesis might have been associated with reduced survival benefit. Individual biomarkers did not comprehensively identify patients who could benefit from therapy; however, multi-parameter models incorporating genomic alteration, immune responses and tumor growth showed promising predictive utility. These results characterize the complex biologic pathways underlying survival benefit from immune checkpoint inhibition in advanced urothelial cancer and suggest that multiple biomarkers might be needed to identify patients who would benefit from treatment