405 results about "Cell targeting" patented technology

The present invention relates to the compositions, methods, and applications of a novel approach to selective cellular targeting. The purpose of this invention is to enable the selective delivery and / or selective activation of effector molecules to target cells for diagnostic or therapeutic purposes. The present invention relates to multi-functional prodrugs or targeting vehicles wherein each functionality is capable of enhancing targeting selectivity, affinity, intracellular transport, activation or detoxification. The present invention also relates to ultra-low dose, multiple target, multiple drug chemotherapy and targeted immunotherapy for cancer treatment.

Described herein are therapeutic targets expressed in cancer stem cells and methods for treating and diagnosing cancer by targeting such cells with antibodies, compounds, nucleic acid, or other therapeutic agent. In one embodiment described herein, therapeutic agents for the treatment of cancer are provided based on the identification of cancer stem cell targets. The present invention also includes therapeutic targets for cancer therapy and cancer stem cell-targeted therapy. The invention includes the treatment of cancer by the administration of compounds or agents that target cancer stem cells.

The present invention relates to compositions and methods for treating diseases, disorders or conditions associated with dysregulated expression of mesothelin. In one embodiment, the invention relates to a fully human chimeric antigen receptor (CAR) wherein the CAR is able to target mesothelin.

The present invention provides methods and compositions for treating various diseases through selective killipg of targeted cells using a combinatorial targeting approach. The invention features protoxin fusion proteins containing a cell targeting moiety and, a modifiable activation moiety which is activated by an activation moiety not naturally operably found in, on, or in the vicinity of a target cell. These methods also include the combinatorial use of two or more therapeutic agents, at minimum comprising a protoxin and a protoxin activator, to target and destroy a specific cell population.

A delivery vehicle is described that is capable of being specifically bound to and taken into targeted cells, delivering numerous physiological agents, particularly paramagnetic ions for magnetic resonance imaging (MRI) of the cells. The delivery vehicle comprises a polymeric molecule having a net positive charge complexed with another polymeric molecule having a net negative charge. Cell targeting moieties and physiological agents, including contrast agents and therapeutic agents, are attached to one or both of the polymeric molecules. In one embodiment, the polymeric molecule having a net negative charge is a nucleic acid. Thus, the delivery vehicles can be used in clinical protocols in which nucleic acids for gene therapy and agents for MRI contrast are co-transported to specific cells allowing medical imaging monitoring of nucleic acid delivery.

The present invention relates to compositions and methods for treating diseases, disorders or conditions associated with dysregulated expression of mesothelin. In one embodiment, the invention relates to a fully human chimeric antigen receptor (CAR) wherein the CAR is able to target mesothelin.

The present disclosure provides compositions and methods that rapidly and selectively modify cells of the immune system to achieve therapeutic objectives. The methods can be practiced in vivo and any cell type that expresses a known marker can be targeted for a therapeutic objective. The present disclosure provides compositions and methods that rapidly and selectively modify cells of the immune system to achieve therapeutic objectives. The methods can be practiced in vivo and any cell type that expresses or is associated with a known marker can be targeted for a therapeutic objective by the modified cell.

In certain aspects, the invention relates to cell delivery compositions comprising a progenitor cell and a targeting moiety, and methods related thereto. Such compositions and methods may be used, for example, in administering a targeted cell therapy to a subject.

The invention relates to a liver cell membrane bionic liposome drug carrier, a preparation method of the liver cell membrane bionic liposome drug carrier, and application of the liver cell membrane bionic liposome drug carrier. The liver cell membrane bionic liposome drug carrier is characterized in that (1) the liposome drug carrier has a cell membrane protein component; (2) the liposome drug carrier is capable of loading drug in vitro, and is used for cell targeting fusion release; (3) the cell membrane protein component of the liposome comes from immortalized human liver cells, and is used for conveying targeted shear plasmids of a hepatitis virus genome; (4) the cell membrane protein component of the liposome comes from an immortalized liver tumor cell line, and is used for targeted drug delivery of liver tumor. The liver cell membrane bionic liposome drug carrier can be used for in vivo targeted hepatic cell transmission and drug delivery of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat) gene targeting plasmids.

The present invention relates to the compositions, methods, and applications of a new approach to pattern recognition based targeting by which an exponential amplification of effector response can be specifically obtained at a targeted cells. The purpose of this invention is to enable the selective delivery of large quantities of an array of effector molecules to target cells for diagnostic or therapeutic purposes. The invention is comprised of two components designated as “Compound 1” and “Compound 2”: Compound 1 is comprised of a cell binding agent and a masked female adaptor. Compound 2 is comprised of a male ligand, an effector agent, and two or more masked female receptors. The male ligand is selected to bind with high affinity to the female adaptor. Compound 1 can bind with high affinity to the target cell and the female receptor can then be unmasked by an enzyme enriched at the tumor cell. The male ligand of Compound 2 can then bind to the unmasked female adaptor bound to the target cell. The masked female adaptor on the bound Compound 2 can then be specifically unmasked. One receptor has in effect become two. Two new molecules of Compound 2 can bind to the unmasked adaptors receptors. After unmasking two receptors in effect become four. The process can continue in an explosive exponential like fashion resulting in enormous amplification of the number of effector molecules specifically deposited at the target cell.

Conformationally constrained peptides that mimic BH3-only proteins and their conjugation to antibodies and other cell targeting compounds, compositions containing the conjugates and their use in the regulation of cell death are disclosed. The conformationally constrained peptides are capable of binding to and neutralising pro-survival Bcl-2 proteins. Processes for preparing the conformationally constrained peptides conjugated to antibodies and other cell targeting compounds and use of the conjugates in the treatment and / or prophylaxis of diseases or conditions associated with deregulation of cell death are also disclosed.

A method for preparing a stable cell-targeting complex comprising a ligand and a cationic liposome encapsulating a therapeutic or diagnostic agent comprises (a) combining the complex with a solution comprising a stabilizing amount of sucrose and (b) lyophilizing the resultant solution to obtain a lyophilized preparation; wherein, upon reconstitution, the preparation retains at least about 80% of its pre-lyophilization activity.

Disclosed is a conjugate comprising a biologically active agent (drug) linked to a subcellular targeting moiety that targets a drug specifically to the nucleus. Targeting is achieved by attaching a steroid hormone (or an analog) to the drug. The steroid hormone attached to the drug binds its corresponding receptor, the formation of the receptor-ligand complex results in the internalization of the complex into the nucleus, thus resulting in nuclear translocation of the drug. Also disclosed is a conjugate (comprising the complex of the drug and the steroid hormone) bound to a polymer by spacers allowing for concurrent passive targeting to the tumor cell (afforded by attachment to the polymer by the EPR effect) and nuclear targeting of the conjugate (due to the presence of the steroid). Using a suitable degradable spacer allows for the release of free drug in the tumor and enhances nuclear targeting efficacy. The polymer can be further linked to a cellular targeting molecule, where the targeting molecule directs the polymer to specific cells. One may thus be able to effectively target drugs to the nucleus of tumor cells. With little or modifications, several therapeutic agents can be targeted using the invention.

The present invention relates to compositions that enhance the intracellular delivery of polynucleotides. The present invention is applicable to the fields of gene therapy and oligonucleotide or DNA therapy. Synthetic methods are disclosed, wherein a polynucleotide can be incorporated into the PEG shielded micelle particle to facilitate the delivery of the polynucleotide across a cellular membrane. Incorporation of the polynucleotide into the shielded micelle particle is provided by covalent and non-covalent means. Other cell targeting agents are provided that may also be covalently coupled to the shielded micelle particle to enhance localization in the body. The compositions herein are suitable for pharmaceutical use but are also suitable as transfection agents for in-vitro or in-vivo research. The PEG shielded polynucleotide micelles can provide favorable pharmacokinetic properties such as enhanced uptake into cancer cells, stability against nucleases, high solubility, and non-binding to serum proteins. The invention comprises a novel gene carrier which is shown to be substantially non-toxic and is suitable for parenteral, oral, pulmonary, and transmucosal delivery of polynucleotides.

The present invention relates to a delivery system that comprises a conjugate that facilitates the delivery of a compound such as a biologically-active macromolecule, a nucleic acid or a peptide in particular, into a cell. The present invention also relates to said conjugate for delivery of a compound, such as a biologically-active macromolecule, a nucleic acid or a peptide, into a cell. The present invention further relates to a pharmaceutical composition comprising said conjugate and to its use. The present invention also relates to a method of delivering a compound to a cell or an organism, preferably a patient. The conjugates comprise: (a) at least one module that mediates cell targeting and facilitates cellular uptake, (b) at least one module that facilitates transport to the endoplasmic reticulum (ER), (c) at least one module that mediates translocation from the ER to the cytosol, and (d) at least one compound to be delivered wherein the modules (a) to (c) and the compound (d) are linked to each other in any arrangement.

A cell-targeted polymeric drug delivery system was designed based on the specific interaction between hyaluronic acid (HA) and its cell surface receptors overexpressed on cancer cell surface. The invention relates to compounds composed of a carrier molecule, 5 wherein the carrier molecule contains at least one residue of an anti-cancer agent and at least one residue of a hyaluronic acid. The invention also relates to methods of making and using the compounds thereof.

The invention relates to the biotechnical field, and concretely relates to a tumor cell targeting penetrating peptide, a polynucleotide molecule and a use thereof, and a targeting drug delivery system containing the tumor cell targeting penetrating peptide. The tumor cell targeting penetrating peptide is characterized in that the tumor cell targeting penetrating peptide contains a CPPs structure domain having cell penetrating peptide activity and an EFG third ring sample mimic peptide structure domain with specific targeting affinity to tumor cells. The tumor cell targeting penetrating peptide has a substantial cell penetrating effect, has the novel characteristics of cell specificity and species specificity, and can be used to diagnose tumor diseases and develop medicines required in the treatment process.

The present invention relates to chimeric proteins with cell-targeting specificity and apoptosis-inducing activities. In particular, the invention is illustrated by a recombinant chimeric protein between human interleukin-2 (IL2) and Bax. The chimeric protein specifically targets IL2 receptor (IL2R)-expressing cells and induces cell-specific apoptosis.

Benzoyl urea derivatives that are alpha helical peptides mimetics that mimic BH3-only proteins, compositions containing them, their conjugation to cell-targeting-moieties, and their use in the regulation of cell death are disclosed. The benzoyl urea derivatives are capable of binding to and neutralizing pro-survival Bcl-2 proteins. Use of benzoyl urea derivatives in the treatment and / or prophylaxis of diseases or conditions associated with deregulation of cell death are also described.

The present invention relates to the compositions, methods, and applications of a novel approach to selective inhibition of several cellular or molecular targets with a single small molecule. More specifically, the present invention relates to multi-functional small molecules wherein one functionality is capable of inhibiting histone deacetylases (HDAC) and the other functionality is capable of inhibiting a different cellular or molecular pathway involved in aberrant cell proliferation, differentiation or survival.

The invention discloses a magnetic nano-grade material with a cell-targeting property, and a biomedical application thereof. The magnetic nano-grade material can be specifically bound with highly expressed transferrin receptors on tissue cell surfaces, and can enter the cells. The material can be bound with various high-transferring-receptor-expression tissue cells with broad spectrum and specificity, such that high-efficiency cell targeting property can be realized on animal models. The material can be used as a magnetic resonance contrast agent and a fluorescent molecular probe in disease diagnosis, and can be used as a medicine carrier in disease treatment.

The present invention relates to chimeric proteins with cell-targeting specificity and apoptosis-inducing activities. In particular, the invention is illustrated by a recombinant chimeric protein between human interleukin-2 (IL2) and Bax. The chimeric protein specifically targets IL2 receptor (IL2R)-expressing cells and induces cell-specific apoptosis.

The present invention is directed to T-cell epitope delivering polypeptides which deliver one or more CD8+ T-cell epitopes to the MHC class I presentation pathway of a cell, including toxin-derived polypeptides which comprise embedded T-cell epitopes and are de-immunized. The present invention provides cell-targeted, CD8+ T-cell epitope delivering molecules for the targeted delivery of cytotoxicity to certain cells, e.g., infected or malignant cells, for the targeted killing of specific cell types, and the treatment of a variety of diseases, disorders, and conditions, including cancers, immune disorders, and microbial infections. The present invention also provides methods of generating polypeptides capable of delivering one or more heterologous T-cell epitopes to the MHC class I presentation pathway, including polypeptides which are 1) B-cell and / or CD4+ T-cell de-immunized, 2) comprise embedded T-cell epitopes, and / or 3) comprises toxin effectors which retain toxin functions.

The invention belongs to the technical field of biomedicine detection, in particular to a method for preparing a nano-fluorescent probe with the quantum dots and an application of the nano-fluorescent probe with the quantum dots on tumor detection. According to the method, aiming at the defects that the traditional preparation method of the quantum dots is complicate to operate and high in cost, a simple and cheap water phase synthetic technique with the quantum dots is provided. The specific synthetic process comprises the synthesis of the water soluble quantum dots, the synthesis of a biocompatible modifier (mPEG) and a tumor cell targeting modifier (cRGD) with the sulfydryl functional groups and a direction reaction between the quantum dots and the two modifiers with the sulfydryl functional groups. According to the method provided by the invention, the preparing raw materials are easy to obtain, the whole preparation process is covalent modification under the conventional condition and the properties of the quantum dots and the modifiers are not changed, and the functions of in vivo long circulation and special cell targeting are simultaneously given for the quantum dots through a one-step reaction, so that the cost is effectively reduced. The modified fluorescent and bright quantum dots obtained by the method are about 5nm in particle size, strong in anti-photo-bleaching property, and have good biocompatibility. The transfection efficiency of the quantum dots on human breast cancer MDA-MB-231 cells can be effectively regulated and controlled by further adjusting the mole ratio of mPEG to cRGD on the surfaces of the quantum dots, so that the nano-fluorescent probe with quantum dots can be applied to the cell fluorescent imaging detection of the tumor targeting.

The invention provides protein subcellular localization assays using split fluorescent protein systems. The assays are conducted in living cells, do not require fixation and washing steps inherent in existing immunostaining and related techniques, and permit rapid, non-invasive, direct visualization of protein localization in living cells. The split fluorescent protein systems used in the practice of the invention generally comprise two or more self-complementing fragments of a fluorescent protein, such as GFP, wherein one or more of the fragments correspond to one or more beta-strand microdomains and are used to “tag” proteins of interest, and a complementary “assay” fragment of the fluorescent protein. Either or both of the fragments may be functionalized with a subcellular targeting sequence enabling it to be expressed in or directed to a particular subcellular compartment (i.e., the nucleus).

The present invention provides methods for stabilizing, reducing or eliminating cancer cells. In particular, the present invention provides prophylactically and / or therapeutically effective regimens for the prevention, treatment and / or management of cancer, the regimens comprising administering one or more cancer therapies to a subject to reduce a cancer cell population. The therapy(ies) in the prophylactically and / or therapeutically effective regimen can be administered at a lower dose than currently used or known to one of skill in the art and / or for a longer period of time and / or more frequently than currently administered or known to one of skill in the art.

The invention discloses a reversible crosslinked biodegradable polymer vesicle having positive charges on an inner membrane, a preparation method thereof and application in preparation of antineoplastic drugs. The biodegradable polymer vesicle based on tumor targeting of a block polymer PEG-P (TMC-DTC)-SP or PEG-P (LA-DTC)-SP, having the positively charged membrane, reversibly crosslinked in reduction sensitivity and intracellularly solvable and crosslinked can effectively support and protect biological macromolecules such as proteins, DNA and siRNA and micromolecular drugs with negative charges in a physical environment and can be delivered to intravital tumor cells to induce apoptosis. The system has lots of unique advantages including simple and easy controllability of preparation, excellent biocompatibility, excellent controlled drug release property, super-strong in-vivo circulation stability, superior cancerous cell targeting and remarkable cancer cell apoptosis capability and the like. Therefore, the reversible crosslinked biodegradable polymer vesicle is expected to become a simple, stable, multifunctional nano system platform integrating multiple advantages and is used for efficient, active and targeted delivery from nucleic acids to in-situ tumors.

The invention belongs to the field of pharmaceutic preparation, and relates to a targeted drug-carrying liposome of a tumor associated fibroblast. The surface of the targeted drug-carrying liposome is modified with a high-affinity ligand of a specific expression protein of the tumor associated fibroblast. The targeted drug-carrying liposome is capable of realizing targeted delivering of drugs into the tumor associated fibroblast, realizing intervention on tumor microenvironment via action on the tumor associated fibroblast, and realizing tumor treatment. And in addition, the tumor associated fibroblast targeted preparation can be combined with routine tumor cell targeted nano preparations so as to improve antitumous effects of the routine tumor cell targeted nano preparations.

This invention provides novel methods and reagents for specifically delivering biologically active compounds to phagocytic mammalian cells. The invention also relates to specific uptake of such biologically active compounds by phagocytic cells and delivery of such compounds to specific sites intracellularly. The invention specifically relates to methods of facilitating the entry of antiviral and antimicrobial drugs and other agents into phagocytic cells and for targeting such compounds to specific organelles within the cell. The invention specifically provides compositions of matter and pharmaceutical embodiments of such compositions comprising conjugates of such antimicrobial drugs and agents covalently linked to particulate carriers generally termed microparticles. In particular embodiments, the antimicrobial drug is covalently linked to a microparticle via a cleavable linker moiety that is non-specifically cleaved in a phagocytic cell. In additional embodiments, the biologically-active compound is provided in an inactive, prodrug form that is activated by a chemical or enzymatic activity specific for cells infected by a microorganism, particularly a pathological or disease-causing microorganism. Thus, the invention provides cell targeting of drugs wherein the targeted drug is only activated in cells infected with a particular microorganism. Alternative embodiments of such specific drug delivery compositions also contain polar lipid carrier molecules effective in achieving intracellular organelle targeting in infected phagocytic mammalian cells. Particular embodiments of such conjugates comprise antimicrobial drugs covalently linked both to a microparticle via a cleavable linker molecule and to a polar lipid compound, to facilitate targeting of such drugs to particular subcellular organelles within the cell. Also provided are porous microparticles impregnated with antiviral and antimicrobial drugs and agents wherein the surface or outside extent of the microparticle is covered with a degradable coating that is degraded within a phagocytic mammalian cell. Also provided are nonporous microparticles coated with an antiviral or antimicrobial drug and further coated wherein the surface or outside extent of the microparticle is covered with a degradable coating that is degraded within a phagocytic mammalian cell. Methods of inhibiting, attenuating, arresting, combating and overcoming microbial infection of phagocytic mammalian cells in vivo and in vitro are also provided.