Multifunctional Scaffolds for Assembling Cancer-Targeting Immune Stimulators Using Chemoselective Ligations.

Chemoselective ligations allow chemical biologists to functionalise proteins and peptides for biomedical applications and to probe biological processes. Coupled with solid phase peptide synthesis, chemoselective ligations enable not only the design of homogeneous proteins and peptides with desired natural and unnatural modifications in site-specific locations but also the design of new peptide and protein topologies. Although several well-established ligations are available, each method has its own advantages and disadvantages and they are seldom used in combination.

A Newly Identified Impurity in Polysorbate 80, the Long-Chain Ketone 12-Tricosanone, Forms Visible Particles in a Biopharmaceutical Drug Product.

Visible particles linked to polysorbates (PSs) used in biopharmaceutical drug products (DPs) have been observed repeatedly in recent years as an industry-wide issue, with PS degradation and insoluble degradation products, especially fatty acids and fatty acid esters, being suspected as root cause. We have shown that the visible particles observed in a monoclonal antibody DP solution in vials after 18 months of long-term storage at 5 ± 3°C were neither linked to reduction in PS (PS80) concentration nor to any known PS degradation product, but consist of 12-tricosanone, an impurity present in the raw material PS80, not a degradation product. The occurrence of visible 12-tricosanone particles in DP correlated with the usage of specific PS80 raw material lots, where 12-tricosanone was found as impurity at elevated levels.

Synthetic integrin-binding immune stimulators target cancer cells and prevent tumor formation.

Immuno-oncology approaches mainly utilize monoclonal antibodies or protein-based scaffolds that bind with high affinity to cancer cells and can generate an immune response. Peptides can also bind with high affinity to cancer cells and are intermediate in size between antibodies and small molecules. They are also synthetically accessible and therefore easily modified to optimize their stability, binding affinity and selectivity.

Synthetic Cancer-Targeting Innate Immune Stimulators Give Insights into Avidity Effects.

Multispecific and multivalent antibodies are seen as promising cancer therapeutics, and numerous antibody fragments and derivatives have been developed to exploit avidity effects that result in increased selectivity. Most of these multispecific and multivalent antibody strategies make use of recombinant expression of antigen-binding modules. In contrast, chemical synthesis and chemoselective ligations can be used to generate a variety of molecules with different numbers and combinations of binding moieties in a modular and homogeneous fashion.