Cross-validation of ELISA and a portable surface plasmon resonance instrument for IgG antibody serology with SARS-CoV-2 positive individuals.

We report on the development of surface plasmon resonance (SPR) sensors and matching ELISAs for the detection of nucleocapsid and spike antibodies specific to the novel coronavirus 2019 (SARS-CoV-2) in human serum, plasma and dried blood spots (DBS)

Dual-Locked Macrocyclic “Turn-On” Drug for Selective and Traceless Release in Cancer Cells

Drug safety and efficacy due to premature drug release in the bloodstream and poor biodistribution remain challenging issues despite seminal advances in the field. To circumvent these limitations, we report a directed-macrocylization as a dual lock for camptothecin (CPT), a small molecule anticancer drug. In this way, the activity is “locked” within the cyclic structure by the redox responsive disulfide and pH-responsive boronic acid-salicylhydroxamate and turned on only in the presence of acidic pH and glutathione through traceless release. Notably the dual-responsive CPT is more active (100-fold) compared to the non-cleavable (closed) analogue. We further include bioorthogonal handle in the cyclic backbone for subsequent functionalization to generate cell-targeting peptide-macrocyclic and protein-macrocyclic CPTs for targeted, traceless drug release in triple negative metastatic breast cancer cells to inhibit cell growth in the low nanomolar concentration

Modular chemical construction of IgG-like mono- and bispecific synthetic antibodies (SynAbs)

In recent years there has been rising interest in the field of protein–protein conjugation, especially related to bispecific antibodies (bsAbs) and their therapeutic applications. These constructs contain two paratopes capable of binding two distinct epitopes on target molecules and are thus able to perform complex biological functions (mechanisms of action) not available to monospecific mAbs. Traditionally these bsAbs have been constructed through protein engineering, but recently chemical methods for their construction have started to (re-)emerge. While these have been shown to offer increased modularity, speed and for some methods, even the inherent capacity for further functionalization (e.g., with small molecule cargo), most of these approaches lacked the ability to include a fragment crystallizable (Fc) modality. The Fc component of IgG antibodies offers effector function and increased half-life. Here we report a first-in-class disulfide re-bridging and click-chemistry-based method for the generation of Fc-containing, IgG-like mono- and bispecific antibodies. These are in the FcZ (FabX)-FabY format, i.e., two distinct Fabs and an Fc, potentially all from different antibodies, attached in a homogeneous and covalent manner. We have dubbed these molecules synthetic antibodies (SynAbs). We have constructed a bispecific T cell-engager (BiTE) SynAb, FcCD20-(FabHER2)-FabCD3, and have confirmed that it exhibits the expected biological functions, including the ability to kill HER2+ target cells in a co-culture assay with T cells