Application of platform process development approaches to the manufacturing of Mabcalin™ bispecifics.

Bispecific biotherapeutics offer potent and highly specific treatment options in oncology and immuno-oncology. However, many bispecific formats are prone to high levels of aggregation and instability, leading to prolonged development timelines, inefficient manufacturing, and high costs. The novel class of Mabcalin™ molecules consist of Anticalin® proteins fused to an IgG and are currently being evaluated in pre-clinical and clinical studies.

Administration of recombinant human placental growth factor decreases blood pressure in obese hypertensive pregnant rats.

Objectives: Although epidemiological studies have shown that obesity is associated with increased incidence of hypertension during pregnancy, the mechanisms linking these two comorbidities are not as well studied. Previous investigations detected lower levels of the anti-hypertensive and pregnancy-related factor, placental growth factor (PlGF), in obese hypertensive pregnancies. Therefore, we examined whether obese hypertensive pregnant rats have reduced PlGF and whether increasing its levels by administering recombinant human (rh)PlGF reduces their blood pressure.

Placental Growth Factor Administration Abolishes Placental Ischemia-Induced Hypertension.

Preeclampsia is a pregnancy-specific disorder of new-onset hypertension. Unfortunately, the most effective treatment is early delivery of the fetus and placenta. Placental ischemia appears central to the pathogenesis of preeclampsia because placental ischemia/hypoxia induced in animals by reduced uterine perfusion pressure (RUPP) or in humans stimulates release of hypertensive placental factors into the maternal circulation.

TLS/FUS: a protein in cancer and ALS.

Comment on: Tan AY, et al. Proc Natl Acad Sci USA 2012; 109:6030-5.

TLS/FUS (translocated in liposarcoma/fused in sarcoma) regulates target gene transcription via single-stranded DNA response elements.

TLS/FUS (TLS) is a multifunctional protein implicated in a wide range of cellular processes, including transcription and mRNA processing, as well as in both cancer and neurological disease. However, little is currently known about TLS target genes and how they are recognized. Here, we used ChIP and promoter microarrays to identify genes potentially regulated by TLS.

TLS inhibits RNA polymerase III transcription.

RNA transcription by all the three RNA polymerases (RNAPs) is tightly controlled, and loss of regulation can lead to, for example, cellular transformation and cancer. While most transcription factors act specifically with one polymerase, a small number have been shown to affect more than one polymerase to coordinate overall levels of transcription in cells. Here we show that TLS (translocated in liposarcoma), a protein originally identified as the product of a chromosomal translocation and which associates with both RNAP II and the spliceosome, also represses transcription by RNAP III.

The TET family of proteins: functions and roles in disease.

Translocated in liposarcoma, Ewing's sarcoma and TATA-binding protein-associated factor 15 constitute an interesting and important family of proteins known as the TET proteins. The proteins function in several aspects of cell growth control, including multiple different steps in gene expression, and they are also found mutated in a number of specific diseases. For example, all contain domains for binding nucleic acids and have been shown to function in both RNA polymerase II-mediated transcription and pre-mRNA splicing, possibly connecting these two processes.