An antibody is an immunoglobulin (Ig) secreted by a plasma cell transformed by B lymphocytes under the stimulation of an antigen, which specifically binds to the corresponding antigen, and each B lymphocyte can only be produced. A proprietary antibody against a specific antigenic determinant.

Antibody development

The development of antibodies is roughly divided into the following three stages:

1.1. Polyclonal antibody:

Polyclonal antibody is obtained by immunizing animals directly with antigens in the early stage ("polyclonal antibodies") when different types of immunoglobulins are contained. Multi-antibody Fab fragments of antigen binding have good safety and therapeutic effects.

1.2 Monoclonal antibody:

In the development of monoclonal antibodies (abbreviated as "mAb"), lymphocyte hybridoma technology is a milestone in the history of antibody development. The monoclonal antibodies produced by hybridoma cells have the characteristics of high specificity, high titer and single structure, and have been widely used in the medical field. In this process, the selection of cell lines is very important, and critical.Ideal cell lines should have the following characteristics: ①Genetic stability.②Be able to expand. ③Can be modified after translation. ④ The antibodies produced are safe for use in humans. Chinese hamster ovary cells are currently most widely used for the preparation of monoclonal antibodies. Because the downstream production also needs to consider the safety of antibody drugs, Chinese hamster ovary cells or human embryonic kidney cells will be the main cells for industrial production of Abs.

1.3 Genetically engineered antibody:

Most of the early therapeutic antibodies are murine antibodies that are susceptible to human anti-mouse antibody response (HAMA). The drawback severely limits the use of murine monoclonal antibodies in humans. With the development of antibody preparation technology, chimeric antibodies, humanized antibodies, and fully human antibodies have been prepared by genetic engineering techniques. The development of genetic engineering has made the preparation of antibody technology into a new era. It has replaced the hybridoma technology and greatly promoted the development and application of antibody drugs. Current methods for the production of fully human antibodies using genetic engineering include phage display technology and transgenic mouse technology.

① Phage display technology: The cDNA of the variable region of human antibody is obtained and cloned into a phage protein gene by polymerase chain reaction (PCR) to express on the surface of the phage. These strains expressing specific antibodies can be screened by antigens. Phage display technology is a new all-human antibody preparation technology that is rapidly evolving in the preparation of genetically engineered antibodies.

②Transgenic mouse technology: the mouse antibody gene is inactivated by gene knockout technology, and the human Ig gene is introduced to replace the mouse Ig gene. The transgenic mouse contains a human antibody gene, and When stimulated by an antigen, the B cells of the mouse can produce human antibody against the antigen. The fully human antibody completely solves the problem of murine origin.

Clinical application of monoclonal antibody

Antibodies can be used not only to treat diseases alone, but also in combination with other drugs. At present, humanized antibodies, all-human monoclonal antibodies and antibody drug conjugates(ADCs) are widely used in clinical applications, and have wide applications in the treatment of tumors, immune diseases, infectious diseases and the like.

2.1 Treatment of tumors

Tumors are a major area of monoclonal antibody therapy, and a large number of antigens have been shown to be expressed higher on tumor cells than normal cells. Most of the traditional chemotherapy drugs used for tumor treatment have toxic side effects. They kill normal cells while killing tumor cells. The antibody drugs are highly specific, so they can bind to disease-specific targets, compared with traditional chemotherapy. In the past decade or so, antibodies have been increasingly effective in treating tumors, and most antibody drugs target antigens on tumors. Monoclonal antibodies are used to treat a variety of human malignancies, and the mechanisms involved are multifaceted, including inhibition of tumor-related signaling pathways, induction of apoptosis, inhibition of angiogenesis, and enhancement of the body's immune response to cancer. A variety of antibodies for treating tumors have been used in the clinic.

2.2 Treatment of autoimmune diseases

Psoriasis patients are often accompanied by scaly erythema, which can cause itching or pain, which has a great impact on the quality of life of patients. Studies have shown that the interleukin-17A (IL-17A) pathway plays a key role in the development of plaque psoriasis, while IL-17A antibodies target the pro-inflammatory factor IL-17A, blocking its binding to receptors and inhibiting inflammatory responses. , thereby reducing the incidence of psoriasis.

2.3 Treatment of infectious diseases

In the early 20th century, serum was often used to treat bacterial infections, but it was often accompanied by immune side effects. At present, many antibody drugs are used in clinical practice, but most of the drugs are aimed at non-infectious diseases. Due to the relatively low efficiency of bacterial resistance and antibacterial drugs, the use of antibodies to treat infectious diseases has renewed interest. There are various methods for treating infectious diseases using antibodies, for example, antibody-conjugated intracellular toxins, antibody-conjugated radionuclides, construction of bispecific antibodies, and the like. At present, antibody treatment of infectious diseases is still in the early stages of research.

2.4 Treatment of cardiovascular disease

Cardiovascular disease is the leading cause of death and disability. How to prevent and treat cardiovascular disease is an urgent problem for clinicians. Low-density lipoprotein cholesterol is known to be a major cause of atherosclerosis and a potential cause of many cardiovascular diseases, and is therefore a major target for disease intervention. Currently recognized statins that reduce low-density lipoprotein cholesterol are a basic treatment for lowering blood fat, but for some patients with high-risk cardiovascular disease (such as familial hypercholesterolemia), the therapeutic effect is not obvious, so new methods for effectively lowering low-density lipoprotein cholesterol are needed.

2.5 Treatment of neurological diseases

The low permeability of the blood-brain barrier and monoclonal antibodies in the brain is the biggest obstacle to the treatment of neurological diseases by antibodies. Most drugs for the treatment are central nervous system diseases are small molecule drugs, but a small number of macromolecular drugs (such as monoclonal antibodies). It is estimated that only 0.1% of the circulating monoclonal antibodies enter the central nervous system. In the blood, the monoclonal antibody receptor prevents its degradation by binding to the monoclonal antibody, thereby maintaining a long half-life, which is though unclear in the nervous system.

Unfortunately there are currently no approved therapeutic antibodies for the treatment of brain diseases such as Alzheimer's disease, Parkinson's disease, which could be a new research focus.

References
[1] Dixit R, Herz J, Dalton R, et al. Benefits of using heterologous Polyclonal antibodies and potential applications to new and undertreated infectious pathogens [J]. Vaccine, 2016, 34 (9): 1152-1161.
[2] Gaughan CL. The present state of the art in expression, production and characterization of monoclonal antibodies[J].Mol Divers, 2016, 20(1): 255-270.
[3] Lonberg N. Fully human antibodies from transgenic mouse and phage display platforms[J]. Curr Opin Immunol, 2008,20(4): 450-459.
[4] Bruggemann M,Osborn MJ, Ma B, et al. Human antibody Production in transgenic animals[J]. Arch Immunol Ther Exp(Warsz), 2015, 63(2): 101-108.
[5] de Goeij BE, Lambert JM. New developments for antibody drug conjugate-based therapeutic approaches[J]. Curr Opin Immunol, 2016, 40: 14-23.

Author's Bio: 

Creative Biolabs provides a full range of services in custom polyclonal and monoclonal antibody production from gene expression or peptide synthesis to antibody purification and labeling.