Autophagy (Auto (self) + phagy (eat)) is a bulk degradation system that degrades and eliminates entire abnormal proteins and old organelles accumulated within cells. When cells are placed under stressful environmental conditions such as starvation, a flat, pouch-like membrane fraction called "isolation membrane" suddenly appears in cytoplasm, bending and extending to wrap cytoplasm and organelles (autophagosome). Then, the autophagosome is fused to lysosomes abundantly containing
proteases and contents of the autophagosome are digested. Amino acids and other substances generated are recycled as a source of nutrients. Originally, autophagy was discovered in yeast. In higher animals, it is involved in not only response to starvation, but also programmed cell death, genesis, aging, manifestation of disease, inhibition of canceration, antigen presentation, and phylaxis.
Companion diagnostics are diagnostic agents used along with therapeutic drugs to distinguish patients on the basis of whether the drug is expected to be effective or who would experience less adverse reactions before administration, or to individually control the dose for each patient. In addition, new drug products can be developed with lower risk and cost in a shorter period of time by narrowing patients down to those for whom the drug is expected to be effective by using companion diagnostics at the development stage of a new drug.
Dengue virus infection is transmitted by Aedes aegypti and Aedes albopictus mosquitoes. There are 4 different types of this virus, and if a person is sequentially infected with different types of the virus, the risk of severe complications may be increased.
EGFRs (epidermal growth factor receptors) are receptors for EGF. When EGF binds to EGFRs, signals are transmitted to cause cell proliferation.
Although the genome of cells comprising an individual body of multicellular organisms is basically identical, cells with different functions in various organs such as liver and muscle are formed from the so-called "memory of cells," which specifies characteristics of individual cells. This memory is called epigenome information. The epigenome information is regulated by DNA methylation and histone modifications, and is renewed during reprogramming from differentiated cells to iPS cells.
Fully human antibodies
Fully human antibodies are derived from human genes.
Therapeutic antibodies recently in use include chimeric
antibodies, humanized antibodies, and fully human antibodies.
Although chimeric antibodies and humanized antibodies contain
approximately 67% and 90%, respectively, of sequences derived
from humans, fully human antibodies are 100% originated from
human genes, and are regarded as safer for use as therapeutic
Fusion partner cells
To establish monoclonal antibodies, antibody-producing cells must be immortalized. One of the commonly used technologies for the immortalization is hybridoma method. This method is based on the antibody production ability of antibody-producing cells and immortal character of fusion partner cells. By fusing these two cells, hybridoma with both antibody production ability and immortal character is established. Generally, hybridoma is instable due to its abnormal genomic number. High performance fusion partner cells are used to improve stability of hybridoma and enhance efficiency of hybridoma establishment.
There are four IgG subclasses in humans, with differences in abilities of passing through the placenta, activating complements, and binding to the Fc site of phagocytes.
Immune system consists of sophisticated mechanisms in which both innate and acquired immunity for host defense against various pathogens. Innate immunity works as primary protection mechanisms to eliminate foreign substances through recognition of characteristic pattern on pathogens. Acquired immunity is more specific immune response against pathogens which are processed by innate immunity. Additionally, acquired immunity can memorize pathogen information to protect from recurrent infections rapidly and efficiently.
Antibodies are also called immunoglobulins, consisting of two heavy chains (H-chain) and two light chains (L-chain). In humans, immunoglobulins are classified into 5 types (IgA, IgD, IgG, IgM, and IgE) based on slight differences in H-chain constant regions. There are 2 types of L-chain, λ-chain and κ-chain. All immunoglobulins have one of the 2 types of the L-chain.
Induced pluripotent stem cells (iPS cells) are artificial pluripotent stem cells which are turned back into undifferentiated state by introducing 4 types of genes (Oct3/4, Sox2, Klf4, and c-Myc) into differentiated somatic cells (reprogramming). In recent years, new technologies have been developed: a technique to produce stem cells without damage to the genome by treating with 3 types of microRNAs present in stem cells (mi-iPS cells), and a direct reprogramming method that can convert human skin cells to nerve cells without using iPS cells. Thus, regenarative medicine is dramatically progressing field of research.
miRNAs are endogenous small RNA strands also transcribed from the genome. miRNAs may control multiple genes by inhibiting translation and degrading mRNA.
When a protein is synthesized based on the information of gene, the information of the gene (DNA) is transcribed to RNA. The initial RNA segments are called "pre-mRNA." The both ends of "pre-mRNA" are modified and only necessary portions are reconnected (splicing) to form mRNA, which leaves from the nucleus to the cytoplasm and being translated to proteins.
Plasma cells, which play impor tant roles in the defense mechanisms against various infectious diseases, produce an enormous number of types of antibodies (immunoglobulin). Many plasma cells are localized in the bone marrow. In multiple myeloma, these plasma cells are transformed into tumor cells and abnormally proliferated. Because only specific immunoglobulin is produced in this disease condition, the variety of antibodies may be dramatically decreased and the susceptibility to infectious diseases may be increased. In addition, symptoms including hypercalcemia, renal disorder, anemia, bone pain and damage, malaise, and shortness of breath can be associated with multiple myeloma.
Neutralizing activity of antibodies refers to the activity of inhibition of target molecules. For neutralization of virus infection, antibodies inhibit viral infection by binding to membrane proteins present on the surface of virus particles.
Rheumatoid arthritis (RA)
RA is an inflammatory autoimmune disease of unknown etiology associated with enlargement and pain in joints of the extremities due to abnormal activity of the immune system, and joint deformity by destruction of cartilage and bone with disease progression. If remaining untreated, the disease may affect patients' daily life. RA is associated with systemic symptoms such as easy fatigability, weakness, body weight loss, and anorexia, and in malignant RA, even vasculitis in the skin, heart, lung, and digestive tract, and fever and cardiac infarction may occur. For diagnosis, rheumatoid factors and anti-CCP antibodies in serum are measured. In addition to nonsteroidal anti-inflammatory drugs, steroids, antirheumatics including methotrexate, immunosuppressive drugs such as tacrolimus, and therapeutic antibodies that can inhibit cytokines, which are a cause of inflammation, are used for treatment. Furthermore, therapeutic antibodies (rituximab) targeting B cells, antibody-producing cells, are also expected to be effective.
Therapeutic antibodies are medicinal products that use antigenantibody response in which an antibody (immunoglobulin) recognizes a specific antigen. Therapeutic antibodies induce overwhelmingly less adverse reactions than conventional chemotherapeutic drugs that attack (react with) normal cells and tissues. In addition, therapeutic antibodies have attracted attention as molecular-targeted drugs with persistent effects because of longer half-life in the body.