What Is an Immunotoxin?

Immunotoxin, also known as biological missile. It is a type of fusion protein specially designed to selectively destroy cells with a specific marker. It is usually formed by chemical cross-linking between a highly specific monoclonal antibody and a powerful toxin molecule.

Traditional immunotoxins are chemical conjugates of monoclonal antibodies and toxic proteins. Anti-tumor monoclonal antibodies are generally mouse monoclonal antibodies and have large molecules. The shortcomings of strong immunogenicity, poor penetrability, and inability to enter human lesions limit its application. Today's recombinant immunotoxins are produced by fusion of a vector and a gene fragment of the toxin through genetic recombination, and are expressed in prokaryotic or eukaryotic cells. They have a small molecular weight, strong penetrating power, weak immunogenicity, and are easily Features of large-scale preparation. At present, the types of immunotoxins are mainly divided according to the "warhead" and the carrier.

Divided according to "warhead": bacterial toxin. Some bacteria can produce powerful toxin proteins, which are currently the largest class of protein toxins used to construct recombinant immunotoxin warheads. These protein toxins are used to link to targeting molecules such as antibodies or growth factors to kill cells with specific antigens or receptors on their surfaces. Because of its targeting and small effective dose (usually a few toxin molecules are enough to kill a cell), it is used in the treatment of autoimmune diseases and transplant rejection; plant toxins. This type of toxin is composed of A chain and B chain, and has strong cytotoxicity and antitumor effect; human-derived protein toxin. The biologically toxic protein toxins are used as warheads for immunotoxins. It can avoid the production of human anti-exogenous toxin antibodies in the human body during the treatment of immunotoxins, making the treatment difficult to continue; double warheads or hybrid warhead toxins. This immunotoxin is a molecule prepared by recombining the genes of two or more different toxins by transgenic methods, and coordinated with different intracellular transport pathways of multiple toxins, thereby effectively improving the cytotoxicity of immunotoxins. . This genetic recombination study. It is more helpful to understand the relationship between the structure and function of various toxins, and also to develop new and more effective immunotoxin warhead molecules;

The killing effect of immunotoxins on target cells usually includes the following steps. Binding: Binding to specific receptor surface antigens on the surface of target cells through antibody or other types of ligands; Internalization: the entry of immunotoxins into cells is the prerequisite for immunotoxins to function; killing target cells: immunotoxins after internalization Apoptosis is induced by inhibiting cancer cell protein synthesis or activating important apoptotic proteins. A class of membrane-active toxins have also been found, which can directly damage cell membranes and cause cell death. It overcomes the shortcomings of poor cytotoxicity caused by the low internalization efficiency of intracellular toxins. So this is a very promising new type of immunotoxin warhead component, which may be more effective in the treatment of solid tumors. ^[2]

Immunotoxin has become one of the hot spots in the field of tumor immunotherapy because of its unique role in killing tumor cells. It has high efficiency, low toxicity and high specificity, and is a unique branch of anti-tumor research. Mainly used in anti-tumor, anti-transplant rejection and treatment of autoimmune diseases.

Immunotoxin tumor-directed therapy

To date, no tumor-specific cell surface markers that can express true differences from normal cells on the surface of tumor cells have been found. However, some molecules on the surface of tumor cells are very different in number compared to normal cells. This relative specificity, coupled with some huge differences in molecular weight, provides guidance-based therapy for tumor cells to minimize the damage to normal cells. Available avenues. In recent years, targeted medicines have gradually attracted worldwide attention. With the advent of monoclonal antibodies (McAb), people have linked anti-tumor monoclonal antibodies and toxins to form an immuno-directed toxin that has both the monoclonal antibody recognition function and the toxin killing function, and can be specific Killing target tumor cells without damaging normal cells opens up a new way for guided therapy of toxins for malignant tumors.

Immunotoxin blood system tumor treatment

Many tumor cells in the blood and bone marrow, usually with high expression of surface markers, can be stable and prolonged contact with the drug, making the immunotoxin treatment method more effective. Most of the immunotoxins in hematological tumors are directed to CD molecules, but also to some ligands, including recombinant immunotoxins constructed with anti-IL-2 receptor subunit (CD25) and CD22 antibody fragments and targets constructed with cytokines Recombinant immunotoxins to recipients, etc., have been well received.

Treatment of Immunotoxin Solid Tumors

Immunotoxin is less effective in treating solid tumors. However, a variety of recombinant immunotoxins targeting solid tumors have been developed and applied. At present, research that is better is targeted at breast cancer, lung cancer, gastric cancer, bladder cancer and central anti-tumor immunotoxins, and some have been applied to clinical treatment of tumors.

Immunotoxin is widely used as a targeted therapeutic drug with a simple structure in the fields of scientific research and treatment, and guided therapy for malignant tumors has achieved great success.

Problems and development directions of immunotoxins

There are also many problems with the currently used immunotoxins, such as the weak specific killing effect on target tissues, especially the poor invasiveness to large solid tumors, and the serious immune response in the body, which makes it difficult to truly transition to clinical applications. Therefore, the development of related immunotoxins that only kill the relevant pathological autoreactive T cells is the key to promote this research. In addition, many immunotoxins cause the same degree of vascular exudation syndrome (VLS) inside the body. Combining the current status of basic and clinical research, the future development of immunotoxins is to use immunotoxins for adjuvant treatment after radiotherapy, chemotherapy and bone marrow transplantation, and to remove small residual lesions in patients; strengthen basic research and develop new types of genetic engineering The recombinant immunotin has the advantages of small molecules, easy diffusion, and low immunogenicity, so as to become one of the important preparations for the treatment of intractable diseases such as tumors.

In recent years, a series of new immunotoxins have emerged that are constructed from membrane-acting toxins. For example, the immunotoxin constructed with melittin, but the research on its application is still in the initial stage, and it cannot replace the classic immunotoxin form in a short time. Therefore, it is important to select antibodies with high specific binding activity and effective internalization. In the construction of immunotoxins, consideration should be given to selecting appropriate construction forms so that the binding of antibodies to antigens is not affected. To obtain highly active immunotoxins, the toxins need to be optimized and modified in many ways. The current research results and clinical trials show that immunotoxins will develop into a new and effective treatment model in tumor targeted therapy. ^[2-3]