Glossary

Glossary

ADLib® System
In the ADLib® system, genetic recombination is activated in antibodies of DT40 cells to increase the diversity of the antibody protein. (DT40 cells are a cell line prepared from chicken cells.) Specific antibodies are then caught like fish with magnetic beads coated with a particular type of antigen. Chiome Bioscience holds the exclusive license to this technology developed by RIKEN. The ADLib® system features superior speed to conventional methods and the ability to obtain antibodies that were difficult to obtain by conventional methods.
Antibody drug
The human body is equipped with a defense system. This system recognizes proteins in bacteria and viruses as foreign substances (antigens) and dispatches proteins that react with the foreign substances (antibodies) to attack these foreign substances. (This is called the “antigen-antibody reaction.”) Drugs employing this natural reaction in humans are called “antibody drugs” (also referred to as “antibody medicines”).
Lead antibody
An antibody that is a candidate to become a drug
Antigen
Antigens are proteins in bacteria and viruses that are usually recognized as foreign substances in the body and elicit antigen-antibody reactions. When antigens enter the body, antibodies are produced to attack and eliminate the antigens. In the context of today’s technology, any substances that bind to antibodies or substances for which someone wishes to produce antibodies may now be called antigens.
Monoclonal antibody
An antibody obtained from a cell that produces a single antibody. Monoclonal antibodies having specific properties can be produced in large quantities and may be used to develop antibody drugs.
Clostridium tetani
The pathogen of tetanus that can infect a person through a cut so small to go unnoticed. In severe cases, tetanus causes general muscular paralysis and tonic seizures. Clostridium tetani, whose spores are commonly found in soil, is an extremely toxic bacterium.
Blockbuster drug
A drug with a therapeutic effect that overturns the current healthcare system and generates huge sales and profits. A common definition of blockbuster drug is annual sales exceeding $1 billion.
Mouse hybridoma method
The most common method for producing monoclonal antibodies. Since animals are used, there are limitations to the amount of antigens that can be used and the range of antigens to which the technique can be applied. In addition, the technique is time-consuming.
Phage display method
A genetic engineering technique for producing monoclonal antibodies. The antigen recognition sites of a diverse array of antibody proteins are expressed and displayed in phage particles and then the phages reacting with the antigen are collected. (Phages are viruses that infect bacteria.) Large amounts of antigen are required and preparation requires large amounts of time because the operation must be repeated multiple times.
Library
A large cell population in which each cell has an antibody with a different structure. A cell library can be likened to a traditional library of books. With the ADLib® system it is theoretically possible to create a cell library with an infinite number of different antibody gene sequences.
DT40 cell
An experimentally immortalized line of B cells collected from the bursa of Fabricius of chickens. (B cells are a type of antibody producing cell; the bursa of Fabricius is a primary immune organ in birds.) A cell population (library) producing a diverse array of antibodies is obtained by artificially activating DNA recombination in the antibody gene locus of the DT40 cell line. This process is the basis of the ADLib® technology.
Trichostatin A (TSA)
A drug used to induce chromatin relaxation in DT40 cells. TSA inhibits a class of enzymes known as histone deacetylase.
Homologous recombination
Homologous recombination is a recombination mechanism occurring in sites of genes with highly similar base sequences. DNA that has been severed by chemical substances or radiation is repaired by homologous recombination. Homologous recombination is a process that is indispensible to the continuation of life. For example, sperm and eggs cannot be formed if homologous recombination does not function properly. Homologous recombination of the antibody gene locus in DT40 cells leads to diversification in antibody genes.
Humanized antibody
An antibody that is similar to a human antibody but retains some structures from another species.
Immunological tolerance
When an organism does not recognize structural components in its own body or antigens having similar structures as “foreign substance.” Because of immunological tolerance, the organism will not show an immune response and produce antibodies against such substances in the organism.
Pathogenic toxins
Toxic substances chiefly produced by organisms such as bacteria. For example, the toxic substance in pathogenic E. coli O157 is a pathogenic toxin.
Immune reaction
A series of physiological reactions by which the body discriminates as to whether an exogenous or endogenous substance is self or non-self and maintains the life of the individual by eliminating the non-self substance.
ADLib® axCELL
A technological application of the ADLib® system. Chiome Bioscience’s proprietary technology for obtaining the antigens used in the ADLib® system from cells. Antibodies that were difficult to obtain by conventional techniques can be obtained by using antigens expressed on the cell surface in their unaltered natural state.
GPCR
GPCR (G-Protein-Coupled Receptor) is a seven-transmembrane protein that is attracting attention as a leading drug target for treating cancer and immune diseases.
Selection
Selecting cells expressing antigen-specific antibodies from a large number of candidate cells.
ADLib® Combo
A technological application of the ADLib® system. Chiome Bioscience successfully developed this method of obtaining antibodies that recognize epitopes that are different from those recognized by existing antibodies. (Epitopes are the part of an antigen recognized by an antibody.)
Ultrahighly diversified ADLib®
A version of the original ADLib® system with increased diversification of the library. What is meant by increasing the diversification of the library is improving the ADLib® system’s library so that it contains antibodies with even more abundant variety. With the ADLib® system, it is theoretically possible to prepare an infinitely large cell population library of different antibody gene sequences. This library can easily be conceived of as an actual library’s book collection, for example. Recent results have indicated that it is possible to obtain specific antibodies for virtually all antigens. Ultrahigh diversification means there is as much as 10 times as much diversification as the diversification of the library of the original ADLib® system.
Chimeric antibody
An antibody in which the antigen-binding part (the variable domain) of an antibody molecule derived from a non-human animal is removed and replaced with the constant domain from a human-derived antibody molecule. Such chimeric antibodies, which are derived from different species, are known to generally retain the ability to bind with antigens that have a variable domain.
High-affinity selection
A method of instantaneous selecting only high-affinity antibodies. To have high affinity means that a substance binds easily with and has a high tendency to bind with another substance.
Fully Human ADLib®
Chiome Bioscience’s original ADLib® system uses avian cells and therefore generates avian antibodies. However, the avian antibody gene sequence can be replaced with a human antibody gene sequence by a molecular biological technique. This operation can be used to construct an ADLib® system that secretes fully human antibodies, making instantaneous human antibody preparation possible.
Ultra-large-scale selection
An iteration of the original ADLib® system in which the original selection scale (volume) is increased around 100 fold (to 50 liters).
Trial contract
A contract made with the client prior to entering a full-scale contract. The client validates and assesses the usefulness of the ADLib® system at this stage before entering into a full-scale contract of intermediate size (around ¥30 million) or large size (a several-year contract for at least ¥100 million).
Optimization
In pharmaceutical research and development, a series of operations for making the necessary improvements in the pharmacokinetics and physical properties of a candidate substance in order to improve safety and therapeutic effect. (Pharmacokinetics refers to the relationship between the effect of a drug and its absorption, distribution, metabolism, and excretion from the body. The physical properties involved relate to method of administration, solubility, stability, and the like.) Humanization is the most important optimization operation in therapeutic antibody R&D.
Nature Biotechnology
An academic journal specializing in biotechnology published by the Nature Publishing Group, the publisher of the journal Nature.
Chromatin structure
Chromatin is a DNA-protein complex present in eukaryotic cells. In humans, for example, the total length of the DNA housed in a single nucleus is said to be about 2 meters. The chromatin structure is the structure that this DNA assumes when housed in a 10-μm nucleus.
Antibody gene locus
A gene locus is the position of a gene on a chromosome or in the genome. An antibody gene locus is the location of a gene forming an antibody in the genome.
IgM
Antibodies are divided into several types according to differences in their structures. IgM is the abbreviation for one of those types (Immunoglobulin M).
Clones
A group of nucleic acids, cells, or individuals having the same origin and uniform genetic information.
ELISA
ELISA (Enzyme-Linked ImmunoSorbent Assay) is an immunochemical assay (see following entry) used to detect and quantify the concentration of antibody or antigen in a sample.
Immunochemical assay
A bioassay (biochemical test) using biological materials, in particular an analytical technique using antibodies. A feature of the immunochemical assay is that the antibody binds to the antigen with extremely high specificity, making the immunochemical assay the most widely used of the bioassay techniques.
First in class antibody
The first specific antibody in the world for a particular target (antigen). First in class antigen candidates come from various types of disease researches, with academia being the principal source.