Expression liabilities in a four-chain bispecific molecule.

Multispecific antibodies, often composed of three to five polypeptide chains, have become increasingly relevant in the development of biotherapeutics. These molecules have mechanisms of action that include redirecting T cells to tumors and blocking multiple pathogenic mediators simultaneously. One of the major challenges for asymmetric multispecific antibodies is generating a high proportion of the correctly paired antibody during production.

Effect of Cigarette Smoking on a Marker for Neuroinflammation: A [C]DAA1106 Positron Emission Tomography Study.

This corrects the article DOI: 10.1038/npp.2017.

Modulation of Macropinocytosis-Mediated Internalization Decreases Ocular Toxicity of Antibody-Drug Conjugates.

AGS-16C3F is an antibody-drug conjugate (ADC) against ectonucleotide pyrophosphatase/phosphodiesterase 3 (ENPP3) containing the mcMMAF linker-payload currently in development for treatment of metastatic renal cell carcinoma. AGS-16C3F and other ADCs have been reported to cause ocular toxicity in patients by unknown mechanisms. To investigate this toxicity, we developed an assay using human corneal epithelial cells (HCEC) and show that HCECs internalized AGS-16C3F and other ADCs by macropinocytosis, causing inhibition of cell proliferation.

Effect of Cigarette Smoking on a Marker for Neuroinflammation: A [C]DAA1106 Positron Emission Tomography Study.

In the brain, microglia continuously scan the surrounding extracellular space in order to respond to damage or infection by becoming activated and participating in neuroinflammation. When activated, microglia increase the expression of translocator protein (TSPO) 18 kDa, thereby making the TSPO expression a marker for neuroinflammation. We used the radiotracer [C]DAA1106 (a ligand for TSPO) and positron emission tomography (PET) to determine the effect of smoking on availability of this marker for neuroinflammation.

Combination Extended Smoking Cessation Treatment Plus Home Visits for Smokers With Schizophrenia: A Randomized Controlled Trial.

Introduction: The majority of people with schizophrenia have a diagnosis of tobacco dependence during their lifetime. A major obstacle to reducing the burden of cigarette smoking in this population is that these smokers have lower quit rates when undergoing standard treatment compared to smokers with no mental illness. We sought to determine if combination extended treatment (COMB-EXT) and home visits (HV) would lead to improved outcomes in smokers with schizophrenia.