WO2011057504A1 - Use of variable lymphocyte receptor (vlr) of agnatha in medicament preparation - Google Patents

Abstract

The invention provides use of variable lymphocyte receptor (VLR) of agnatha for preparing medicament, especially for preparing the medicament for diagnosing or resisting pathogenic microorganism infection and tumor.

Description

 Application of the non-mandibular vertebrate variable lymphocyte receptor (VLR) in pharmacy

 Technical field

 The invention relates to the use of a substance, namely a non-mandibular vertebrate variable lymphocyte receptor (VLR) Use in pharmaceuticals, especially in the manufacture of anti-pathogenic microorganisms, anti-tumor therapeutic drugs and diagnostics.

 Background technique

 Antibacterial drugs are one of the most widely used and widely used drugs in clinical practice and play an important role in the prevention and treatment of infectious diseases. However, with the massive abuse of antibacterial drugs, the resistance of pathogenic microorganisms to antibacterial drugs is spreading. In the treatment of infected patients with antibacterial drugs, there are often cases where the drug is ineffective. To solve this problem effectively, on the one hand, it is necessary to increase the intensity of control of the abuse of antibacterial drugs, and on the other hand, new antibacterial drugs are urgently needed to supplement.

Traditionally, traditional anti-tumor drugs are generally classified into plant alkalis, anti-metabolisms, antibiotics, alkylating agents, hormones, and antibodies. At present, the commonly used anti-tumor drugs have exceeded 80. Kind. In recent years, monoclonal antibody and small molecule tyrosine kinase inhibitor drugs have promoted the development of anti-tumor drugs, and the growth rate of new drugs is much higher than that of traditional drugs. However, at present, the share of new drugs in the market in China is still low, and traditional drugs are still widely used in clinical practice.

 The round-mouthed animal is also known as the non-mandibular vertebrates, which mainly include the seven major categories of the seven-spotted and blind-streaked. Variable lymphocyte receptor (VLR) It is a novel receptor found in non-mandibular vertebrates. Mandibular vertebrates achieve their own specific immunity through antibodies, while non-mandibular vertebrates pass the variable lymphocyte receptor (VLR) Realize your own specific immunity. Variable lymphocyte receptor (VLR) refers to the variable lymphocyte receptor (VLR) The gene is randomly inserted into a leucine-rich repeat unit to form a diverse antigen recognition receptor, which specifically recognizes different antigens and achieves adaptive immunity of the jawless vertebrates. Variable lymphocyte receptor (VLR) It can be expressed on the surface of lymphocytes of vertebrate-free vertebrate, and secreted VLR, which can be secreted into serum. The secretory VLR is a tetramer or pentamer formed by 4 to 5 dimers linked by disulfide bonds. They have 8 to 10 antigen binding sites, respectively. Morphologically, there is a high degree of similarity to higher mammalian IgM. Variable lymphocyte receptor (VLR) affinity for specific antigens IgG The class of antibodies is ten times higher. Its unique characteristics are expected to be applied in anti-microbial infection and anti-tumor diagnosis and treatment like antibody drugs and even better than antibody drugs. To date, no variable lymphocyte receptor (VLR) has been observed. Used in the pharmaceutical field.

 Summary of the invention

 The present invention finds a variable lymphocyte receptor (VLR) produced by lymphocytes secreted by a vertebrate-free vertebrate It has potential application value in anti-pathogenic microbial infection and anti-tumor treatment and diagnosis. Immunostimulating non-mandibular vertebrates with foreign antigens (such as pathogenic microorganisms, tumor antigens, etc.), and obtaining high-affinity, high-specificity variable lymphocytes capable of recognizing and binding specific microorganisms and tumor antigens through genetic engineering and protein engineering Cell receptor (VLR). This receptor is ten times more affinitive than the IgG class antibody produced by higher mammals. Therefore, the variable lymphocyte receptor (VLR) recognizes and neutralizes Microbiologically, it has stronger specificity and sensitivity than antibodies, and will play a role in the diagnosis and anti-microbial treatment of pathogenic microbial infections. At the same time, under the immune stimulation of specific tumor antigens, this receptor acts on tumor antigens. Its superior affinity makes it a new ideal tool for targeted cancer therapy and diagnosis.

 detailed description

 Immunization of non-mandibular vertebrates with exogenous antigens (eg pathogenic microorganisms, tumor antigens, etc.), extraction of immunized animal lymphocyte cDNA, from Cloning of variable lymphocyte receptor (VLR) genes in cDNA, screening for high-affinity, high-specificity VLRs that recognize and bind to specific microbes or tumor antigens by yeast cell or phage display technology Genes, and reuse DNA recombination technology to achieve mass production of VLR and its recombinant proteins through prokaryotic or eukaryotic protein expression systems. To meet the needs of industrial pharmaceutical raw materials.

 The application of the non-mandibular vertebrate variable lymphocyte receptor (VLR) in pharmaceuticals mainly includes the following aspects:

 1, combined with biomarker technology, such a VLR Receptors can be used in assembly in vitro diagnostic kits for the diagnosis of pathogenic microbial infections and for tumor discovery, efficacy and prognosis of tumor markers, because their affinity for antigens is ten times higher than that of antibody molecules, so it will It has higher sensitivity and detection specificity than traditional antibody-based diagnostic kits.

 2, VLR The recombinant protein and the recombinant protein can be combined with the high specificity and high affinity of the microorganism, and have a neutralizing effect on the microorganism, can prevent the microbial invasion and promote the degradation and elimination thereof, thereby achieving the therapeutic effect.

 3, VLR and its recombinant protein have a high specific binding capacity to tumor cells. Will VLR In combination with drugs, enzymes or radioisotopes, VLRs are automatically guided to bind to specific tumor cells or tissues in the body and produce therapeutic effects by the drugs they carry. VLR It has better affinity and specificity than monoclonal antibodies, can accurately target and capture target cells, react specifically with target targets, and will act as a biological missile to achieve unique and superior performance that other drugs cannot achieve. .

Claims (1)

1. The application of the non-mandibular vertebrate variable lymphocyte receptor (VLR) in pharmaceuticals, characterized by including VLR And its recombinant protein application in pharmaceuticals. 2. The use of a variable lymphocyte receptor (VLR) according to claim 1 for pharmaceutical use, characterized in that a variable lymphocyte receptor (VLR) The use in the diagnosis of pathogenic microbial infections and the manufacture of anti-pathogenic microbial drugs. 3. The use of a variable lymphocyte receptor (VLR) according to claim 1 for pharmaceutical use, characterized in that a variable lymphocyte receptor (VLR) It is used in the diagnosis and manufacture of anti-tumor drugs for tumor diseases.