The key to technology is how to acquire antibodies that bind to antigens of target diseases including cancers and immune diseases.
We acquire highly functional antibodies through utilizing flexibly the phage display method and the hybridoma method according to the characteristics of the target and further combining our own antibody screening method. We also utilize the single B-cell screening method as a new screening technology.
Phage display method
This is a method to produce antibodies in a test tube without using animals. Using this method, we can acquire unique antibodies which are difficult to acquire in the hybridoma method. Examples of such antibodies include those against the biological and non-biological targets including autoantigens, and those against biological targets of highly toxic substances.
Human antibody library
Our human antibody library has excellent diversity so that we can expect it to contain antibodies against various antigens.
Creation of libraries is a significantly important technological element, as the more excellent the types and characteristics of antibodies contained in the library, the higher the probability of isolating good antibodies. We have produced excellent antibodies against various antigens through establishing 100 billion of antibodies library from human naïve B-cells with our own methods.
We will create new antibody libraries and develop screening methods to isolate the target antibodies efficiently through utilizing our technology and knowledge.
Camel antibody library
Camel antibodies (VHH antibodies) have unique structure called single chain antibody, different from human antibodies. They are easy to produce due to the small size and are characterized by the high thermal stability. Therefore, they are expected to be utilized not only as medical drugs or reagent for research but also for a wide variety of applications including materials to capture antigens in filters and other industrial products.
We have created libraries of VHH antibodies with such excellent features from camel immune cells and have been proceeding with development to meet various needs for antibodies.
Antibody screening technology (ICOS method)
As we use antigen/antibody reaction to acquire antibodies, firstly we need antigens as targets.
Proteins as target antigens are on the surface of cell membrane, forming complex folded structure.
Usually, purified proteins, extracted from cell membrane, are used in development of MABs. With such purified protein, however, it is extremely difficult to reproduce the same complex structure as it was on the membrane.
Thus, an alternative came up to use a cell itself as a material. This method, however, causes nonspecific reaction (absorbance) occurs, resulting in plenty of unwanted antibodies mixing. A solution for this problem is the ICOS method, which has an effect to remove nonspecific absorbance during screening using a living cell. This method has enabled acquiring highly affinitive antibodies reflecting the steric structure of protein on the cell membrane. We have been developing the best screening technology for the targets that are difficult to obtain in a usual immune method, so that we can acquire antibodies for various targets including small molecules efficiently.
Target Discovery (Phenotypic analysis)
On the surface of disease-related cells such as tumor cells, molecules specific to the disease may be expressed.
We find useful antibodies by screening our antibody library against such targets.
Strength of this method is to be able to reflect the cell conditions due to direct targeting of a cell. It is expected as a method to discover new targets, different from the conventional mRNA expression analysis method.
Hybridoma method
Hybridoma method is a widespread technology to acquire cells that produce monoclonal antibodies that bind to specific antigens only. When animals are immunized, immune cells called B-cells come to produce antibodies that bind to the injected antigens (usually proteins). Due to biological instability of B-cells and difficulty in cultivation, it was difficult to mass-produce antibodies. So, infusing a B-cell with a myeloma, an immortal cancer cell that multiplies limitlessly, is invented to create hybridoma that has both characteristics.
Hybridoma can produce antibodies while multiplying limitlessly, which has enabled mass production of monoclonal antibodies that used to be difficult.
Antibody designing
Antibody sequences obtained from hybridomas or phage libraries can be used to engineer antibodies in various ways, including humanization/chimerization (when the hybridoma method is used), isotype conversion, and conversion to antibody fragments such as Fab and scFv. These sequences can also be applied to CAR-T. Antibodies converted in various forms can be used in diverse modalities according to medical needs.
Single B-cell screening method
Single B-cell screening method isolates B-cells that produce antibodies reacting to specific antigens only to acquire monoclonal antibodies.
Using this method, we can specify very rare antibody producing cells correctly and efficiently, which enables us to acquire antibodies with significantly high specificity. Also, we can acquire various antibodies with high throughput by obtaining antibody genes from the plenty of acquired B-cells. As we can generate antibody-producing cells using the acquired antibody genes, we can produce even monoclonal antibodies of animal species with high difficulty in creation of hybridoma.
Glossary
| Camel antibody |
An antibody originated from a camel. Different from human antibodies, they have only H chains, having merits including small molecule size and physical stability.
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| Naïve B-cell |
”Naïve” means that the B-cell has not been stimulated by any antigen. After stimulated, it will produce antibodies against the specific antigen. |
| Specificity |
A characteristic of an antibody that it binds to a specific antigen only. |