Design and Evaluation of Phosphonamidate-Linked Exatecan Constructs for Highly Loaded, Stable, and Efficacious Antibody-Drug Conjugates.

Topoisomerase I (TOP1) Inhibitors constitute an emerging payload class to engineer antibody-drug conjugates (ADC) as next-generation biopharmaceutical for cancer treatment. Existing ADCs are using camptothecin payloads with lower potency and suffer from limited stability in circulation. With this study, we introduce a novel camptothecin-based linker-payload platform based on the highly potent camptothecin derivative exatecan.

Compact hydrophilic electrophiles enable highly efficacious high DAR ADCs with excellent PK profile.

The recent success of antibody-drug conjugates (ADC), exemplified by seven new FDA-approvals within three years, has led to increased attention for antibody based targeted therapeutics and fueled efforts to develop new drug-linker technologies for improved next generation ADCs. We present a highly efficient phosphonamidate-based conjugation handle that combines a discrete hydrophilic PEG-substituent, an established linker-payload and a cysteine-selective electrophile in one compact building block. This reactive entity provides homogeneous ADCs with a high drug-to-antibody ratio (DAR) of 8 in a one-pot reduction and alkylation protocol from non-engineered antibodies.

Intestinal transgene delivery with native E. coli chassis allows persistent physiological changes.

Live bacterial therapeutics (LBTs) could reverse diseases by engrafting in the gut and providing persistent beneficial functions in the host. However, attempts to functionally manipulate the gut microbiome of conventionally raised (CR) hosts have been unsuccessful because engineered microbial organisms (i.e.

Large Particle 3D Concrete Printing-A Green and Viable Solution.

The Large Particle 3D Concrete Printing (LP3DCP) process presented in this paper is based on the particle bed 3D printing method; here, the integration of significantly larger particles (up to 36 mm) for selective binding using the shotcrete technique is presented. In the LP3DCP process, the integration of large particles, i.e.

Interpreting time-series COVID data: reasoning biases, risk perception, and support for public health measures.

Effective risk communication during the COVID-19 pandemic is critical for encouraging appropriate public health behaviors. One way that the public is informed about COVID-19 numbers is through reports of daily new cases. However, presenting daily cases has the potential to lead to a dynamic reasoning bias that stems from intuitive misunderstandings of accumulation.