Many laboratories have utilized cell-free systems or prokaryotic systems designed to produce biological molecules with single polypeptide chains, limited folding requirements, and without glycosylation. The yeast systems are used to generate glycoproteins; however, their glycosylation profiles are vastly different from those of mammalian cells. Without significant glycoengineering, the yeast-produced recombinant glycoproteins may be unsuitable as therapeutic molecules. As such, the use of mammalian cells is still the preferred method to produce complex biological molecules…
Category: <span>Biologics Production</span>
Directed evolution has profoundly changed the way antibodies or antigen binding fragments (Fab) are produced today. Lead generation for product candidates is oftentimes based on complex combinatorial libraries containing a large collection of variant antibodies. The selection of candidate molecules by screening procedures like phage display is considered the gold standard. One major advantage of these methods is that initial candidate molecules can be further improved in terms of affinity, specificity, etc. by reiterative in vitro maturation processes using the very methods that have been used for lead generation…
ImmBio’s lead development candidate is an influenza vaccine based on the ImmunoBody® platform technology. An ImmunoBody is a fusion of a selected immuno-dominant antigen with a cell-binding domain — the Fc fragment of human IgG1. The use of recombinant Fc fusion proteins is well documented where it can help solubilize hydrophobic proteins, provide a handle for easy detection and purification, as well as improve half-life…
Preliminary studies with a variety of cell-based vaccines suggest target accessibility (potential immunogenicity) to immune-directed approaches in a variety of solid tumors. However, four primary factors limit the generation of effective immune-mediated anticancer activity in therapeutic applications: 1) identifying and/or targeting cancer-associated immunogen(s) (target) in an individual patient; 2) insufficient or inhibited level of antigen-presenting cell (dendritic cell, macrophage) priming and/or presentation; 3) suboptimal T cell activation (potency) and proliferation; and 4) cancer-induced inhibition of the anticancer immune response in both afferent and efferent limbs…
We have designed a novel autologous vaccine by combining two vaccine strategies that have each been previously tested in separate non-small cell lung cancer (NSCLC) clinical trials: 1) a GM-CSF gene transduced tumor cell vaccine; and 2) a TGFβ2 antisense gene transduced cell vaccine. Each has demonstrated similar beneficial effects without any evidence of significant toxicity in advanced cancer patients…
Microbial fermentation is used to produce such products as therapeutic proteins, antibiotics, hormones, enzymes, amino acids, blood substitutes and alcohol. These products may be expressed by the microbial cells themselves, expressed intracellularly in the cytoplasm or, in the case of bacterial cells, in the periplasmic material. Before any intracellularly-produced molecules can be used and further purified, the cells (i.e., E. coli) must be concentrated and set in an appropriate buffer (cell washing) before being lysed. Then after lysis, molecules of interest have to be separated from the parent cells and then clarified to remove cellular debris and other contaminants. Depending on the process used, additional clarification steps may be necessary…
A considerable clinical need exists for alternatives to the autologous vein and artery tissues used for vascular reconstructive surgeries such as coronary artery bypass graft (CABG), lower limb bypass, arteriovenous shunts, and repair of congenital defects to coronary circulation. So far, devices made from synthetic materials have not matched the efficacy of native grafts, particularly in small diameter applications. Recent advances in cell biology and tissue engineering have introduced the possibility of a living, biological graft that might mimic the functional properties of native vessels…
Regulatory agencies routinely announce changes in the GMP (Good Manufacturing Practices) norms and quality standards designed to guarantee that every product retains characteristics required for its pharmaceutical use.The alignment with emerging regulatory requirements is mandatory, therefore, to assure production process consistency, as well as the safety and efficacy of the finished product…
Incorporating a genomic regulatory sequence element can help to develop a robust expression vector, leading to improved recombinant protein expression in cultured cells. Such elements include the Expression Augmenting Sequence Element (EASE), scaffold- or matrix-attachment regions (S/MAR elements), Insulators, or the Universal Chromatin Opening Element (UCOE). However, generating a robust vector further requires having the relevant vector components in a context-optimized manner…
Today, technology has reached a point where organisms (bacteria, plant and animal cells) can be genetically engineered to produce specific macromolecules and perform complex chemical reactions. Hence, they are called “cellular factories.” Cellular factories have applications in: biomedicine (e.g., implanted insulin secreting cells for the management of diabetes); biotechnology (recombinant protein and enzyme production for pharmaceutical and food industries); bioremediation (toxic waste and pollutant clean-up); green chemistry (production of chemicals with minimum toxic bi-product generation); alternative energy generation (electricity and hydrogen production by bacteria); biosensors (e.g., devices housing “canary cells”, which can signal the presence of pollutants, viral agents, or toxic chemicals); bioreactive devices (that can detect low concentrations of chemicals, etc.)…