A single-domain antibody (sdAb, also called Nanobody) is an antibody fragment consisting of a single monomeric variable antibody domain. Like a whole antibody, it is able to bind selectively to a specific antigen. With a molecular weight of only 12–15 kDA, single-domain antibodies are much smaller than common antibodies (150–160 kDa). They have been shown to be just as specific as a regular antibody and in some cases more robust. They are being researched for multiple pharmaceutical applications in in vivo imaging and targeted therapy. eg. the fusion of a fluorescent protein to a single-domain antibody can be used to trace targets in different compartments of living cells. They can therefore increase the possibilities of live cell microscopy and will enable novel functional studies.

TIGIT:CD155/CD112 immune inhibition (in green)

We previously addressed the PD-1:PD-L1/PD-L2 immune inhibition and the corresponding cell-based tools to screen immuno-oncology agents for restoring antitumor immune response. Unfortunately cancer cells have other ways to escape and survive. Let’s look together at another immune inhibition pathway, namely the TIGIT:CD155/CD112.

The islets of Langerhans are the regions of the pancreas that contain its endocrine (i.e., hormone-producing) cells. Discovered in 1869 by German pathological anatomist Paul Langerhans, the islets of Langerhans constitute approximately 1% to 2% of the mass of the pancreas. There are about one million islets distributed throughout the pancreas of a healthy adult human. Each is separated from the surrounding pancreatic tissue by a thin fibrous connective tissue capsule. The islets of Langerhans contain beta cells, which secrete insulin, and play a significant role in diabetes.

Islets are widely used for transplantation to restore beta cell function from diabetes, offering an alternative to a complete pancreas transplantation or an artificial pancreas. Because the beta cells in the islets of Langerhans are selectively destroyed by an autoimmune process in type 1 diabetes, islet transplantation is a means of restoring physiological beta cell function in patients with type 1 diabetes.

Human Islets for Research (HIR)® are primary human islets processed from organ donor pancreases that have been approved for research but not for clinical transplantation of either the  pancreas or the isolated islets. HIR® are obtained in a proprietary process of pancreas digestion and islet purification that results in uniformly high quality HIR® for delivery to diabetes  investigators. Quality Control (QC) testing is routinely performed prior to release to assure uniform quality and function of these islets available for research.

Messenger RNAs – a promising class of new therapeutic biologics

As messenger RNAs (mRNAs) are easier to deliver into cells than plasmids or viral vectors, they are useful for non-dividing cells. Inversely to the vectors, they ensure genome integrity that is recommended for cell therapeutics. mRNA are also well adapted to transient expression as required for cellular reprogramming, gene editing, and vaccines.

You might like to take a look at this poster, presented by Trilink (renowned modified nucleic acid experts) at the Keystone symposia last March (Pattern Recognition Signaling: From Innate Immunity to Inflammatory Disease). They share results on how to optimize messenger RNA for therapeutic activity.

“Innate Immune focused approaches to maximize messenger RNA therapeutic activity”
Download your copy of the poster here.