Toolkit to Examine Lifelike Language v.2.0: Optimizing Speech Biomarkers of Neurodegeneration.

Introduction: The Toolkit to Examine Lifelike Language (TELL) is a web-based application providing speech biomarkers of neurodegeneration. After deployment of TELL v.1.

Evaluating the Potential of Cyclodextrins in Reducing Aggregation of Antibody-Drug Conjugates with Different Payloads.

Cyclodextrins (CDs) are versatile agents used to solubilize small drugs and stabilize proteins. This dual functionality may be particularly beneficial for antibody-drug conjugates (ADCs), as CDs may "mask" the hydrophobicity of the drug payloads. In this study, we explored the effect of CDs on the physical stability of ADCs composed of the same antibody but with different payloads (maytansinoid, auristatin, and fluorophore payloads).

"Negative" Impact: The Role of Payload Charge in the Physicochemical Stability of Auristatin Antibody-Drug Conjugates.

Antibody-drug conjugates (ADCs) tend to be less stable than their parent antibodies, which is often attributed to the hydrophobic nature of their drug payloads. This study investigated how the payload charge affects ADC stability by comparing two interchain cysteine ADCs that had matched drug-to-antibody ratios and identical linkers but differently charged auristatin payloads, vcMMAE (neutral) and vcMMAF (negative). Both ADCs exhibited higher aggregation than their parent antibody under shaking stress and thermal stress conditions.

Features in Backgrounds of Microscopy Images Introduce Biases in Machine Learning Analyses.

Subvisible particles may be encountered throughout the processing of therapeutic protein formulations. Flow imaging microscopy (FIM) and backgrounded membrane imaging (BMI) are techniques commonly used to record digital images of these particles, which may be analyzed to provide particle size distributions, concentrations, and identities. Although both techniques record digital images of particles within a sample, FIM analyzes particles suspended in flowing liquids, whereas BMI records images of dry particles after collection by filtration onto a membrane.

Agitation-Induced Aggregation of Lysine- And Interchain Cysteine-Linked Antibody-Drug Conjugates.

Drug conjugation to an antibody can affect its stability, which depends on factors such as the conjugation technique used, drug-linker properties, and stress encountered. This study focused on the effects of agitation stress on the physical stability of two lysine (ADC-K) and two interchain cysteine (ADC-C) conjugates of an IgG monoclonal antibody (mAb) linked to either ∼4 MMAE or DM1 payloads. During agitation, all antibody-drug conjugates (ADCs) exhibited higher aggregation than the mAb, which was dependent on the conjugation technique (aggregation of ADC-Ks > ADC-Cs) and drug-linker (aggregation of ADCs with MMAE > ADCs with DM1).