47 results about "Chlorotoxin" patented technology

This invention includes compositions and methods for combination chemotherapy, particularly involving at least one chemotherapeutic agent used in combination with chlorotoxin or a derivative thereof.

Chlorotoxin-labeled nanoparticles that target primary brain tumors, compositions that include the nanoparticles, methods of imaging tissues using the nanoparticles, and methods for treating tissues using the nanoparticles.

Disclosed is a method of treating cell proliferative disorders, such as cancer, with low doses of chlorotoxin and / or derivatives, analogs or fragments thereof, which are effective to inhibit or arrest abnormal cell growth.

Methods and systems for discovering drug candidates are disclosed. Methods and systems can include generating libraries of potential drug candidates (e.g., libraries of peptides) that can be screened to identify sub-libraries of potential drug candidates (e.g., sub-libraries of peptides) having selected pharmacological properties. Methods of making and using peptide libraries are also provided. D-amino acid chlorotoxins and D-amino acid chlorotoxin variants are also provided.

The present invention provides fusion proteins for the detection and treatment of neuroectodermal tumors. Previous work demonstrated that chlorotoxin is specific for glial-derived or meningioma-derived tumor cells. The current invention has extended the use of chlorotoxin-cytotoxin fusion proteins to treat the whole class neuroectodermal tumors such as gliomas, meningiomas, ependymonas, medulloblastomas, neuroblastomas, gangliomas, pheochromocytomas, melanomas, PPNET's, small cell carcinoma of the lung, Ewing's sarcoma, and metastatic tumors in the brain. Also, diagnostic methods are provided for screening neoplastic neuroectodermal tumors.

Disclosed is a method of diagnosing and treating myeloproliferative or lymphoproliferative cell disorders, such as cancer, with chlorotoxin and / or derivatives, analogs or fragments thereof, which are effective to bind to an inhibit abnormal myeloid or lymphoid cell growth.

The present invention relates to the use of a toxin moiety (e.g., a chlorotoxin moiety) as a carrier for therapeutic agents, e.g., therapeutic agents that require intracellular uptake to exert their effects. For example, in some embodiments, the present invention provides conjugates comprising a toxin (e.g., a chlorotoxin) moiety and an anti-cancer moiety and methods for using such conjugates to increase cellular uptake and / or increase specificity for cancer cells of the anti-cancer drug. In some embodiments, the present invention provides conjugates comprising a toxin moiety (e.g., a chlorotoxin moiety) and a nucleic acid agent. Also provided are methods of treatment involving administration of such conjugates, and pharmaceutical compositions and kits useful for carrying out such methods of treatment.

Specific drug delivery to tumor cells without affecting normal cells is a major challenge in cancer treatment. The present invention incorporates embedding nonionic surfactant vesicles (niosomes) containing an anti-cancer therapeutic agent with chlorotoxin into a thermosensitive chitosan hydrogel network. Chitosan has mucoadhesive property which can be used in the targeting of the tumor cells with the mucin over expression. Chlorotoxin is a 36 amino acid peptide obtained from Leiurus quinquestriatus scorpion venom which binds preferentially to tumor cells of neuroectodermal origin but not to normal cells. The incorporation of chlorotoxin along with niosomes in the chitosan hydrogel is used as the second targeting strategy to further improve the specific delivery of drugs to tumor cells such as glioma.

A method for preparing a CTX (Chlorotoxin)-targeted oxidized graphene nanometer material comprises the following steps: 1, mixing graphite and H2SO4-HClO4, stirring and mixing the mixture in an ice-bath, continuing stirring in a warm water bath , heating to 100 to 120 DEG C for deacidification, diluting to 800 to 1000 ml and then centrifuging, adding an alkali solution and then mixing and settling, stirring at 70 to 90 DEG C and filtering under the condition of being hot, washing to be approximately neutral, and freeze drying at minus 40 DEG C under the vacuum condition to obtain oxidized graphene; 2, mixing the oxidized graphene with a phosphate buffer solution, adding N-Hydroxysuccinimide and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride to perform an activating reaction at room temperature; adjusting the pH value of the mixture to be 7.0 to 8.0, adding CTX for reaction, centrifugating and washing the obtained product, and performing vacuum freeze drying at minus 40 DEG C to obtain the CTX-targeted oxidized graphene nanometer material. The material can be used for transporting an anticancer drug of adriamycin to a brain glioma in a targeted manner.

The invention belongs to the field of chimeric antigen receptor cells, and particularly relates to a coding amino acid sequence of a bispecific chimeric antigen receptor targeting human CLTX-R and NKG2DL, an immune response cell modified with the coding amino acid sequence as well as a preparation method and application of the immune response cell. The invention relates to a bispecific chimeric antigen receptor of a bispecific targeting human NKG2DL and chlorotoxin receptor (CLTX-R) protein or a functional variant thereof, an immune response cell modified with the bispecific chimeric antigen receptor, as well as a preparation method and application of the bispecific chimeric antigen receptor. The obtained novel functionalized immune response cell can effectively target and attack various tumors, and can be used for preparing a preparation for treating malignant tumors. The immune response cell modified with the bispecific chimeric antigen receptor targeting CLTX-R and NKG2DL can enhance the binding with tumor cells, and obviously enhances the anti-tumor activity.

The invention belongs to the field of biotechnology, which relates to a tumor targeting magnetic resonance contrast medium modified by chlorotoxin and a preparation method and application thereof. Highly branching characteristics of cationic tree-like macromolecular materials are utilized, a large number of Gd3+ is connected onto the surface of the tumor targeting magnetic resonance contrast medium modified by the chlorotoxin, signal intensity of magnetic resonance imaging (MRI) diagnosis is improved, and diagnosis drug dosage is reduced. Besides, tumor targeting head base-chlorotoxin (CTX) extremely having clinical application potential is utilized to modify the cationic tree-like macromolecular materials, gathering of the Gd3+ at the tumor position is improved, MRI signals at the tumor position are enhanced, and sensitivity and accuracy of the tumor diagnosis are improved. Compared with the existing commercial micromolecule gadolinium-class contrast media, the tumor targeting magnetic resonance contrast medium modified by the chlorotoxin is high in relaxation rate, small in dosage and capable of enhancing the MRI signals at the tumor position in a targeting mode, improving signal contrast between the tumor position and normal tissue, effectively prolonging observable time of the MRI signals at the tumor position simultaneously and facilitating accurate tumor diagnosis.

The invention belongs to the technical field of biology, and relates to a chlorotoxin-modified glioma targeting gene delivery compound and a preparation method thereof. In the invention, chlorotoxin is modified onto a cationic high polymer material through a hydrophilic polymer, and is compounded with a plasmid DNA (Deoxyribonucleic Acid) under an electrostatic action, so that a gene delivery compound is formed. Due to the adoption of the gene delivery compound, the transfection efficiency and expression level of a gene in a glioma cell can be effectively increased; and in particular, after administration is performed in a non-invasive intravenous injection way, so that the gene expression of the gene delivery compound in a glioma lesion location is remarkably improved. The chlorotoxin-modified glioma targeting gene delivery compound in the invention can be used for transfecting endothelial cells, epithelial cells, various tissue parenchyma cells and / or nerve cells derived from human bodies and animals.

The invention relates to the technical field of medical imaging technology, in particular to a targeted-imaging agent used for detecting glioma and preparation method and application of the targeted-imaging agent. The targeted-imaging agent refering to <18>F-fluorobenzoic acid-chlorotoxin has the advantages that boundaries of the glioma can be accurately defined; high sensitivity is achieved due to the fact that the chlorotoxin marked with <18>F can be subjected to imaging detection via PET (positron emission tomography) and focus 6mm in size can be detected with the PET which is much higher than SPECT (single photon emission computed tomography) in image resolution; a brand new direction is provided for diagnosis the glioma, and important clinical value in aspects of early diagnosis of the glioma, boundary define of the glioma, therapeutic evaluation, targeted drug delivery and the like is achieved; the targeted-imaging agent can be applied to the PET, the boundaries of the glioma can be accurately defined, high image resolution can be realized, the focus 6mm in size can be detected, and the PET is much higher than the SPECT in the image resolution in the prior art.

The invention provides a fusion protein gold nano-cluster complex Au@(gCTX)NCs and a preparation method and an application thereof. The technical scheme provided by the invention comprises that a recombinant chlorotoxin protein GST-CTX(gCTX) having a glioma targeting function is used as a template, and the multifunctional chlorotoxin-gold nano-cluster fluorescence complex is synthesized; at the same time, the invention relates to a preparation method of a protein gold nano-cluster complex, and also relates to the tumor targeting specificity of the chlorotoxin-gold nano-cluster fluorescence complex and use of the chlorotoxin-gold nano-cluster fluorescence complex in tumor diagnosis and treatment.

The inventors propose to label a chlorotoxin with I-123 or I-124 for a diagnostic agent, and with I-124 or I-131 for a therapeutic agent to reduce tumors and then to use a process they previously invented to stabilize the radiopharmaceutical. The inventors propose to reconstitute the preferred agents and administer them cyclically to diagnose and treat tumors. The inventors also propose a TETA or DOTA link to a metal radioisotope.

The invention discloses a folded chlorotoxin, a chlorotoxin mutant, a folded chlorotoxin mutant and a preparation process thereof. The peptide sequence of the folded chlorotoxin is MCMPCFTTDHQMARKCDDCCGGKGRGKCYGPQCLCR-NH2. The peptide sequence of folded chlorotoxin mutant is MCMPCFTTDHQMARSCDDCCGGSGRGSCYGPQCLCR-NH2, and the folded chlorotoxin mutant is formed by replacing lysine (Lys, K) inside the peptide sequence of the chlorotoxin with serine (Ser, S). According to the preparation process disclosed by the invention, the potential application value of the chlorotoxin and a ramification thereof in biology and pharmacy can be extended, and good economic benefit and social benefit on the aspects of lift health, individual medical treatment and the like can be achieved.

The present invention is directed to methods and methods for the treatment, inhibition and / or reduction, and detection of metastatic tumors. In some embodiments, the inventive methods include systemic (e.g., intravenous) administration of a chlorotoxin agent that may or may not be labeled. In some embodiments, the inventive methods allow treatment, inhibition and / or reduction, and detection of metastases in the brain. In some embodiments, neovascularization is inhibited and / or newly formed vessels are caused to regress.

The invention provides chimeric antigen receptor(s) (CAR(s)) that comprise a fusion protein of CTX or any functional variant thereof or a CTX-like peptide or any functional variant thereof as the extracellular antigen recognition moiety of the CAR. CAR(s) comprising CTX, a CTX-like peptide or functional variants of the foregoing are collectively referred to herein as “CTX-CAR(s).” Such CTX-CAR(s) may further comprise additional moieties or domains in the extracellular domain, a transmembrane domain and at least one intracellular! signaling domain. Such CTX-CAR(s) may be expressed in a host cell, such as, but not limited to, an immune effector cell. The present invention also provides methods of treatment (such as, for example, methods for treating cancer) by providing to the patient in need thereof immune effector cells that are engineered to express a CTX-CAR described herein.

The present invention provides an anti-tumor targeting complex which is a chemical crosslinked complex CTX-Onc obtained from chlorotoxin and onconase through disulfide bond crosslinking. Compared with existing anti-tumor CTX and Onc mixtures, the anti-tumor targeting complex of the invention shows better anti-tumor effects both at a cellular level and an animal tumor model level, and has good clinical application and development prospects. The invention also provides a method for preparing the complex and applications of the complex in the preparation of antitumor drugs.

The present invention discloses a gene-engineered targeting anti-glioma Acp-W1 protein, a preparation method and applications. The present invention separates out a protein, the sequence of which is an amino acid sequence shown as SEQ ID No: 1. Primers related to genetic engineering insert the nucleotide sequence of chlorotoxin into an expression vector pGEX-6p-1, so that a recombinant expression plasmid is formed; the recombinant expression plasmid transforms colon bacillus Rossetta (DE3), and after cell lysis, the Acp-W1 protein is produced by affinity chromatography, ultrafiltration, desalination and chromatography purification. The Acp-W1 protein has specific targeting effect on gliomas, can effectively inhibit the proliferation of rat gliomas and has targeting anti-glioma effect. The Acp-W1 protein is applicable to the preparation of drugs treating or preventing gliomas. The preparation method of the present invention has the advantages of simplicity, convenient operation, high output and good biological activity.

The invention relates to the technical field of polypeptide synthesis, in particular to a preparation method of chlorotoxin. According to the method, chlorotoxin is prepared through a process of combining solid-phase fragment synthesis and liquid-phase synthesis, and the chlorotoxin is divided into four fragments of 1-5, 6-9, 10-13 and 14-36 for segmented coupling. The method is simple and convenient to operate, and the synthesis period of the process is greatly shortened. Through the solid-liquid combined synthesis method, the yield and purity of chlorotoxin are improved, side reactions and types of by-products are reduced, the total yield can reach 25% or above, and the purity reaches 99% or above.

The present invention provides formulation / composition comprising phytonutrients with natural chlorotoxins for targeting cancer, infection, inflammation and pain without any side effects and a method for synthesizing the same. The raw materials are cleaned and dried and to prepare coarse powder of 40 mesh size, extracted with solvent (comprising water: alcohol in a ratio of 40:60) in a ratio of 4:1 with overnight soaking. Prior to cold extraction, the mixture is macerated for 4 hours. The mixture is refluxed for 2 hours at 80° C. The addition of ethanol, maceration and refluxing steps are repeated three times and above solvent is added, if required. The residue is checked for complete extraction after every refluxing step. The extract / residue is filtered and concentrated under vacuum. The extract / residue is vacuum tray dried at 70-80° C. for 12 hours. The extract / residue is scraped and dried lumps of the extract / residue are milled. Additional natural product powders are added to the milled powder. The final extract / residue is sieved and packed.