66 results about "Tumor vasculature" patented technology

The present invention relates generally to methods and compositions for targeting the vasculature of solid tumors using immunological- and growth factor-based reagents. In particular aspects, antibodies carrying diagnostic or therapeutic agents are targeted to the vasculature of solid tumor masses through recognition of tumor vasculature-associated antigens, such as, for example, through endoglin binding, or through the specific induction of endothelial cell surface antigens on vascular endothelial cells in solid tumors.

The present invention provides a conjugate containing a therapeutic agent linked to a homing molecule that selectively homes to tumor vasculature and selectively binds collagen such as non-helical collagen or collagen IV. In one embodiment, the conjugate contains a homing peptide or peptidomimetic that includes the amino acid sequence CREKA (SEQ ID NO: 1) or a conservative variant or peptidomimetic thereof.

Disclosed herein are immunogenic compositions, methods of designing immunogenic compositions, methods of treatment using immunogenic compositions, methods of evaluating cell-mediated immunity resulting from immunogenic compositions, research models, and methods of making research models, all of which relate to targeting tumor vasculature.

Disclosed are new phosphatidylserine binding constructs with surprising combinations of properties, and a range of diagnostic and therapeutic conjugates thereof. The new constructs effectively bind phosphatidylserine targets in disease and enhance their destruction, and can also specifically deliver attached imaging or therapeutic agents to the disease site. Also disclosed are methods of using the new construct compositions, therapeutic conjugates and combinations thereof in tumor vasculature targeting, cancer diagnosis and treatment, and for treating viral infections and other diseases.

Disclosed are surprising discoveries concerning the role of anionic phospholipids and aminophospholipids in tumor vasculature and in viral entry and spread, and compositions and methods for utilizing these findings in the treatment of cancer and viral infections. Also disclosed are advantageous antibody, immunoconjugate and duramycin-based compositions and combinations that bind and inhibit anionic phospholipids and aminophospholipids, for use in the safe and effective treatment of cancer, viral infections and related diseases.

The present invention provides erythrocytes or nucleated erythrocyte precursors from animals or patients with SS or SA hemoglobin or erythroleukemia cells stably transfected with BCAM / Lu which are capable of selectively localizing in tumor vasculature promoting ischemia and occlusion and carrying oncolytic viruses, antitumor proteins, plasmids, toxins and chemotherapy into the tumor milieu. Nucleated erythroid precursors containing SS or SA hemoglobin and transfected with nucleic acids encoding a hypoxia-responsive element and containing nucleic acids encoding expression of oncolytic viruses, superantigens, toxins, viruses, antitumor proteins and chemotherapy are also useful in inducing a potent and specific tumoricidal response. An especially favored carrier is an SS nucleated erythroid precursor transfected with a replication competent oncolytic adenovirus or self-replicating alphavirus expressing a fusogenic membrane glycoprotein or a tumoricidal polypeptide.

The invention relates to the field of medicines, specifically to an integrin blocker which inhibits generation of tumor vasculature and has integrin endophilicity and binding capacity. The blocker is a polypeptide. The integrin blocker polypeptide can be used to treat solid tumor. The integrin blocker can be applied in the preparation of medicines for treating tumor. The sequence of the integrin blocker is Ala-Cys-Asp-Cys-Arg-Gly-Asp-Cys-Phe-Cys-Gly-Gly-Gly-Gly-Ile-Val-Arg-Arg-Ala-Asp-Arg-Ala-Ala-Val-Pro (the sequence contains two disulfide bonds and the pairing manner is 1-4 and 2-3). The invention is characterized in that the tumor origins from primary or secondary cancer and sarcoma of human head and neck, brain, thyroid, pancreas, lung, liver, oesophagus, stomach, mammary gland, kidney, gallbladder, colon or rectum, ovary, uterus, cervix, prostate, bladder and testis. According to the invention, treatment spectrum of the integrin blocker is greatly expanded, novel thinking and prospect are provided for drug development, and the integrin blocker polypeptide AP25 has substantial social value and market value.

The instant invention provides methods for treating a solid tumor in a subject comprising modulating nitric oxide production in the tumor to normalize tumor vasculature and administering an anti-tumor therapy to the subject. The invention further provides methods of treating a solid tumor in a subject comprising selectively increasing cyclic guanosine monophosphate (cGMP) or cGMP dependent protein kinase G production in the tumor vasculature to an amount effective to normalize tumor vasculature and administering an anti-tumor therapy to the subject.

Disclosed are various compositions and methods for use in achieving specific blood coagulation. This is exemplified by the specific in vivo coagulation of tumor vasculature, causing tumor regression, through the site-specific delivery of a coagulant using a bispecific antibody.

Disclosed are surprising discoveries concerning the role of anionic phospholipids and aminophospholipids in tumor vasculature and in viral entry and spread, and compositions and methods for utilizing these findings in the treatment of cancer and viral infections. Also disclosed are advantageous antibody, immunoconjugate and duramycin-based compositions and combinations that bind and inhibit anionic phospholipids and aminophospholipids, for use in the safe and effective treatment of cancer, viral infections and related diseases.

Embodiments of the invention are directed methods that include a thymidine kinase deficient vaccinia virus. The methods include administering the vaccinia virus at increased viral concentrations. Further aspects of the invention include methods for inducing oncolysis or collapse of tumor vasculature in a subject having a tumor comprising administering to a subject at least 1×108 infectious viral particles of a TK-deficient, GM-CSF-expressing, replication-competent vaccinia virus vector sufficient to induce oncolysis of cells in the tumor.

The present invention provides methods of immunizing a subject against a tumor, inhibiting tumor growth, inhibiting tumor recurrence, treating, suppressing the growth of, or decreasing the incidence of a tumor, overcoming tolerance to a tumor vasculature marker (TVM) in a subject comprising the step of administering a vaccine comprising a TVM or a nucleic acid encoding a TVM and related vaccines. The present invention also provides a method of targeting a tumor vasculature in a subject having a tumor comprising the step of contacting said subject with a labeled compound that binds a) a tumor vasculature marker (TVM) or b) a nucleic acid molecule encoding said TVM.

The present invention provides erythrocytes or nucleated erythrocyte precursors from animals or patients with at least one S hemoglobin allele which are capable of selectively localizing in tumor vasculature resulting in vaso-occlusion, hemolysis and heme release. A tumoricidal effect is achieved when these cells are administered in before during or after administration of (i) an agent(s) that interferes with degradation of reactive oxygen species, (ii) impairs glucose uptake and / or (iii) chemotherapy. These cells also carry oncolytic viruses, antitumor proteins, multidrug resistant proteins, chemotherapy, monoclonal antibodies, superantigens, superantigen conjugates and fusion proteins, siRNAs, plasmids and non-protein toxins and attenuated tumoricidal bacterial cells specifically into the tumors and induce a tumoricidal effect.

The present invention concerns compositions and methods for the treatment of cancer. More specifically, the present invention relates to identification of aminopeptidase A (APA) as a functional target in neo-vasculature, e.g., tumor vasculature; the present invention also relates to targeting peptides and antibodies specific for APA which may be used for cancer therapies.

The present invention includes a method and apparatus for tumor blood vessel obstruction and tumor therapy. The embolic device is made of biocompatible materials. The embolic device may utilize thrombus-enhancing filamentary material and / or coagulate components that enhance the effectiveness to cause tumor vasculature thrombosis. The specific design of the device will facilitate tumor vasculature site space-filling. The embolic device may be implanted into the targeted tumor vasculature site by minimal invasive method.

The invention belongs to a field of medicinal preparations, and relates to a liposome drug delivery system used for tumor imaging, wherein the system is modified by a polypeptide with an amino acid sequence of RPAKPAR and wraps a near-infrared fluorescent dye. According to the invention, the RPAKPAR polypeptide is a targeting head group and modified on surface of stealth liposome, and wraps the near-infrared fluorescent dye. After intravenous administration, through mediation effect of the RPAKPAR polypeptide, the carrier stealth liposome actively sends the near-infrared fluorescent dye to tumor positions, and penetrates tumor vasculatures into whole tumor tissues, thereby increasing distribution of the dye in the tumor positions; and then by using an in-vivo optical molecular imaging technology, the tumor imaging with relatively high fluorescent signal intensity can be provided.

Embodiments of the invention provide for cell therapy for cancers having a TEM1 or TEM8 antigen. Certain embodiments provide for cell therapy that targets tumor vasculature, including the tumor vascular bed, for example. In specific embodiments, TEM1- and / or TEM8-specific chimeric antigen receptors are employed.

The present invention provides erythrocytes or nucleated erythrocyte precursors from animals or patients with at least one S hemoglobin allele which are capable of selectively localizing in tumor vasculature resulting in vaso-occlusion, hemolysis and heme release. A tumoricidal effect is achieved when these cells are administered in before during or after administration of (i) an agent(s) that interferes with degradation of reactive oxygen species, (ii) impairs glucose uptake and / or (iii) chemotherapy. These cells also carry oncolytic viruses, antitumor proteins, multidrug resistant proteins, chemotherapy, monoclonal antibodies, superantigens, superantigen conjugates and fusion proteins, siRNAs, plasmids and non-protein toxins and attenuated tumoricidal bacterial cells specifically into the tumors and induce a tumoricidal effect.

Polypeptides and proteins that specifically bind to and immunologically recognize CD276 are disclosed. Chimeric N antigen receptors (CARs), anti-CD276 binding moieties, nucleic acids, recombinant expression vectors, host cells, populations of cells, pharmaceutical compositions, and conjugates relating to the polypeptides and proteins are also disclosed. Methods of detecting the presence of (a) cancer or (b) tumor vasculature in a mammal and methods of (a) treating or preventing cancer or (b) reducing tumor vasculature in a mammal are also disclosed.

The invention relates to a preparation method of targeting tumor vasculature Anxa1 marked precursor NOTA-IF7, which belongs to the fields of organic chemistry and medicines. According to the invention, a double-function chelating agent 1,4,7-triazacyclononane-1,4,7- triaceticacid (1,4,7-triazacyclononane-1,4,7- triaceticacid, p-SCN-Bn-NOTA, NOTA for short) is coupled with specifically combined tumor vasculature 7 peptide amino acid (isoleucine-phenylalanine-leucine-leucine-tryptophan-glutamine-arginine, IF7), and a HPLC one-step method is used for purifying to obtain NOTA-IF7. THE preparation method of NOTA-IF7 is simple, the reaction condition of the technology is mild, the yield is high, the product can be used for isotope mark of fluorine-18, copper-64 and gallium-68, and is conveniently prepared to a positron photographic developer for tumor.

Compositions and methods useful for delivery of targeted therapies for pulmonary arterial hypertension, sepsis, cancer and cachexia. The compositions and methods are based on peptide pharmacophores that selectively bind to and home to diseased tissue and enable targeted therapies to affect a beneficial therapeutic result. Peptide pharmacophores may selectively target tumor vasculature, regenerating tissue, wounded tissue, inflamed tissue, fibrotic tissue, remodeled tissue, tissue characterized by elevated heparanase levels, and have the ability to internalize into such diseased cells.

The present invention provides, inter alia, methods for treating or ameliorating the effects of a disease, such as cancer, in a subject. The methods include: administering to a subject in need thereof (a) a therapeutically effective amount of a monoclonal antibody or antigen binding fragment of the present invention, and (b) a therapeutically effective amount of a combination therapy including bevacizumab and at least one additional therapeutic agent; or a therapeutically effective amount of at least one additional therapeutic agent selected from the group consisting of a COX-2 inhibitor (COXIB), a non-steroidal anti-inflammatory drug (NSAID), a prostaglandin E2 (PGE2) synthase inhibitor, and combinations thereof. Compositions, including pharmaceutical compositions, and kits for treating diseases, such as cancer, are also provided herein.

The present invention relates to method and means for treating a solid tumor using a number of, in vitro prepared, anticellular agent(s)-carrying blood platelets to induce a thrombus formation within the tumor vasculature, and at the same time to deliver a high concentration of an anticellular agent within the tumor. The blood platelets are targeted and attached to the tumor vasculature using in vivo assembled binding complexes, each having at least one binding site specifically binding to tumor cells or to tumor-associated vasculature, and at least one binding site specifically binding to a blood platelet surface. The platelet-mediated thrombus formed within the tumor vasculature leads to occlusion of the tumor vasculature, with ultimate destruction of the centrally located tumor cells. This is followed by destruction or impairing the growth or cell division of the peripherally located tumor cells, by the anticellular agent(s) carried by the blood platelets.