Antibody News

Therapeutic proteins such as monoclonal antibodies (mAbs) can be subject to physical or chemical stress during the manufacturing process and supply chain. A common chemical degradation is the deamidation of the amino acid asparagine to aspartic acid or iso-aspartic acid. Modification of glutamine to glutamic acid is also possible, although this occurs at a slower rate. When deamidation occurs in the antigen binding region of the mAb, it can result in a loss of potency. This sequence liability may be defined as a critical quality attribute and represents a risk to the development of novel biologics and biosimilars alike.  As such, it is important to have reliable protein characterization methods with sufficient sensitivity and selectivity to identify and quantify levels of deamidation.

Physicochemical analysis

The transformation of an amide side-chain, via a succinimide intermediate, to a carboxylic acid results in a change in the net charge of the...

By Jamshed Arslan Pharm.D.

Interneurons transmit impulses between other neurons, in part, to facilitate the birth of neurons. Cortical interneurons themselves arise from the progenitors in the ventral telencephalon, a brain region that generates basal ganglia. The role of mechanistic target of rapamycin (mTOR) signaling in this process is poorly understood even though mTOR is known to determine brain size. By deleting mTOR in mouse interneuron progenitors and their progeny, Dr. Woo-Yang Kim’s team at the University of Nebraska Medical Center, USA found two homeostatic activities of mTOR in...

By Yoskaly Lazo-Fernandez, PhD

The first description of what is called today an autophagosome was given in a paper published in 1957. Its author employed electron microscopy to observe the neonatal features of mouse kidneys¹. Autophagosomes where then described as large round bodies found in the cytoplasm, primarily of proximal tubule epithelial cells, and consisting of an amorphous material containing concentrically lamellar structures and mitochondria. It was not by chance that these structures were found in kidney tubules, because autophagy plays an essential role in kidney function both in health and disease^2,3. This blog will briefly introduce the main...

By Jamshed Arslan Pharm.D.

Muscle atrophy is a common feature of many tumors. Cancer-induced muscle wasting, or cancer cachexia, results from pro-inflammatory cytokines (TNFα and IL-6) and/or agonists of type IIB activin receptors (ActRIIB), but the key humoral factors have remained elusive. Animal studies have implicated systemic inflammation-induced activation of p38β MAPK-C/EBPβ signaling, but the etiology of cancer cachexia was unclear until recently. A team led by researchers at the University of...

By Yoskaly Lazo-Fernandez, PhD

The cell surface receptor CD95 (also known as Fas or APO-1) is the best-characterized member of the tumor necrosis factor (TNF) receptor superfamily¹. Many receptors in this family, including CD95 are called Death Receptors because of their ability to induce apoptosis². In cells expressing CD95, apoptosis is triggered by the binding of this receptor’s specific ligand, CD95L. This mechanism, which was originally discovered in the early nineties, allows CD95L...

By Christina Towers, PhD.

It has long been known that programmed cell death can take place in many forms.  The most well characterized form, apoptosis, occurs when either extrinsic or intrinsic stimuli stimulate signaling cascades that result in a series of caspase cleavage events resulting in cleavage and activation of the effector caspase-3.  The end result is cell shrinkage, condensation and cleavage of chromosomal DNA, and plasma membrane blebbing that leaves the cell membrane intact¹.  Apoptotic cells are engulfed by antigen presenting cells and induce anti-inflammatory and tolerogenic immune responses².  Alternatively, necroptosis, a programmed form of necrosis, is less characterized.  However, it is now known that this process is also tightly regulated and mediated by a complex...

By Christina Towers, PhD

Autophagy is an important cellular process that facilitates the degradation of damaged cytoplasmic material and toxic protein aggregates. Its role in neuronal function is apparent by the neurodegenerative phenotypes observed in autophagy deficient genetic mouse models. Mice with neuron-specific knock out of the core autophagy protein, ATG7, are viable but most go on to develop behavioral defects and eventually massive neuronal loss in the cerebral corticies¹.

But perhaps the most causative links between autophagy and neurological functioning have been observed in animal models of progressive neurodegenerative diseases including Alzheimer’s, Parkinson’s, and Huntington’s disease. Each of these devastating diseases is characterized by a build-up of toxic protein aggregates: β-...

By Christina Towers, PhD

Apoptosis, or programmed cell death, is the result of an intricate cascade of signaling events that is initiated by extrinsic (death receptor mediated) and intrinsic (mitochondrial mediated) stimuli.  Extrinsic apoptosis is initiated by ligand binding to death receptors followed by signaling cascades that activate caspase-8, also known as the initiator caspase.  The effector caspase-3 can be activated by caspase-8, but is usually activated downstream of the intrinsic pathway, and often the extrinsic pathway will converge on the intrinsic for more efficient programmed cell death. Intrinsic signaling takes place on the mitochondrial membrane, where BH-3 only proteins activate mitochondrial outer membrane permeabilization (MOMP) and the release of mitochondrial proteins like cytochrome c.  Subsequently, the apoptosome is formed by a...

By Christina Towers, PhD

A critical mechanism that cells use to generate nutrients and fuel metabolism is through a process called autophagy.  This process is complex and involves over 20 different proteins, most of which are highly conserved across species.  It involves the formation of a double membrane structure known as an autophagasome that fuses with the lysosome to facilitate the degradation of cytoplasmic material.  While bulk autophagy is thought to be largely non-specific, clearing damaged proteins from the cytoplasm, recent studies have begun to highlight more selective forms of autophagy.  Selective autophagy, also coined organellophagy, facilitates the degradation of specific organelles that are damaged or targeted for recycling.  Thus far, researchers have begun to investigate the selective degradation of mitochondria, peroxisomes, endoplasmic reticulum (ER), nuclei, and chloroplasts in plants, all mediated through variant forms of...

By Bethany Veo, PhD

Necroptosis occurs when cells fail to undergo apoptosis following inflammatory, oxidative or ischemic stressors. Necroptotic cell death removes damaged cells and cells no longer critical for development, independently of caspase activation.  Whereas apoptotic cells display condensed nuclei and fragmentation, the telltale signs of necroptosis are plasma membrane permeabilization and mitochondria swelling.  As a regulated cell death mechanism, the process of necroptosis is necessary for maintaining cellular homeostasis during development and as a response to cellular stress conditions.  

Initiation of necroptosis results from blocking pro-survival cues from inhibitors of apoptosis.  Signaling through TNFa (tumor necrosis factor), FASL (FAS ligand) and TRAIL (Tumor...

By Christina Towers, PhD

Autophagy is an evolutionarily conserved process that cells use to break down damaged cytoplasmic constituents in order to fuel cellular metabolism, particularly in instances of stress. This process has been heavily implicated in a variety of diseases, most noteworthy are neurological disorders and cancer. The role of autophagy in cancer is context dependent and somewhat controversial¹. It was originally suggested by Dr. Beth Levine's group that autophagy is tumor suppressive, a claim supported by loss of the core autophagy gene, BECN1, in many tumor types including breast, prostrate, and ovarian². However, critics of this notion point out the important observation that BECN1 is adjacent to the heavily deleted tumor suppressor gene, BRCA1,...

Autophagy is an essential process that cells utilize to degrade and recycle damaged material and fuel metabolism, especially under stress.  The process is evolutionarily conserved and complex, relying on over 20 key proteins. Induction of autophagy is mediated by the formation of the