Evaluating Antibody Pharmacokinetics as Prerequisite for Determining True Efficacy as Shown by Dual Targeting of PD-1 and CD96.

One important prerequisite for developing a therapeutic monoclonal antibody is to evaluate its in vivo efficacy. We tested the therapeutic potential of an anti-CD96 antibody alone or in combination with an anti-PD-1 antibody in a mouse colon cancer model. Early anti-PD-1 treatment significantly decreased tumor growth and the combination with anti-CD96 further increased the therapeutic benefit, while anti-CD96 treatment alone had no effect.

Increased brain penetration and potency of a therapeutic antibody using a monovalent molecular shuttle.

Although biotherapeutics have vast potential for treating brain disorders, their use has been limited due to low exposure across the blood-brain barrier (BBB). We report that by manipulating the binding mode of an antibody fragment to the transferrin receptor (TfR), we have developed a Brain Shuttle module, which can be engineered into a standard therapeutic antibody for successful BBB transcytosis. Brain Shuttle version of an anti-Aβ antibody, which uses a monovalent binding mode to the TfR, increases β-Amyloid target engagement in a mouse model of Alzheimer's disease by 55-fold compared to the parent antibody.

The SpoMBe pathway drives membrane bending necessary for cytokinesis and spore formation in yeast meiosis.

Precise control over organelle shapes is essential for cellular organization and morphogenesis. During yeast meiosis, prospore membranes (PSMs) constitute bell-shaped organelles that enwrap the postmeiotic nuclei leading to the cellularization of the mother cell's cytoplasm and to spore formation. Here, we analysed how the PSMs acquire their curved bell-shaped structure.

Cytokinesis in yeast meiosis depends on the regulated removal of Ssp1p from the prospore membrane.

Intracellular budding is a developmentally regulated type of cell division common to many fungi and protists. In Saccaromyces cerevisiae, intracellular budding requires the de novo assembly of membranes, the prospore membranes (PSMs) and occurs during spore formation in meiosis. Ssp1p is a sporulation-specific protein that has previously been shown to localize to secretory vesicles and to recruit the leading edge protein coat (LEP coat) proteins to the opening of the PSM.

Identification of neurotoxic chemicals in cell cultures.

In order to identify the neurotoxic potential of drugs or chemicals in vitro, a combination of different in vitro cell culture tests is required. Depending on the type and use of a given test compound, a sequential exposure of freshly isolated and cultured hepatocytes and chicken brain cells is suitable. In order to find out more about the stability of liver-derived metabolites, co-cultures are appropriate.

Differential requirement for phospholipase D/Spo14 and its novel interactor Sma1 for regulation of exocytotic vesicle fusion in yeast meiosis.

During sporulation and meiosis of budding yeast a developmental program determines the formation of the new plasma membranes of the spores. This process of prospore membrane (PSM) formation leads to the formation of meiotic daughter cells, the spores, within the lumen of the mother cell. It is initiated at the spindle pole bodies during meiosis II.

Development of hepatocyte cultures in toxicity testing.

The liver plays a key role in drug and xenobiotic metabolism. The probability of detecting the toxicity of unknown chemicals in vitro is therefore highest in liver cell cultures. In culture however, enzymes involved in xenobiotic metabolism are preferentially degraded within one to two days.