142 results about "Host immunity" patented technology

The present invention features PD-1 binding proteins, a subset of which inhibits binding of PD-L1 to the PD-1 receptor. These binding proteins can be employed to modulate the immune system through the manipulation of the PD-1 signaling pathway, enhancing host immunity to treat infections and cancer.

A method and pharmaceutical composition are provided for enhancing the endogenous immune response-mediated elimination of a population of pathogenic cells in a host animal wherein the pathogenic cells preferentially express, uniquely express, or overexpress a binding site for a particular ligand. The invention comprises administering the ligand conjugated to an immunogen to a host animal harboring the population of pathogenic cells. Antibodies, preexisting or administered to the host animal to establish a passive immunity, directed against the immunogen bind to the ligand-immunogen conjugate resulting in elimination of the pathogenic cells by the host's immune response. At least one additional therapeutic factor is administered selected from the group consisting of a cell killing agent, a tumor penetration enhancer, a chemotherapeutic agent, antimicrobial agent, a cytotoxic immune cell, and a compound capable of stimulating an endogenous immune response wherein the compound does not bind to the ligand-immunogen conjugate.

Novel activating receptors of the Ig super-family expressed on human myeloid cells, called TREM(s) (triggering receptor expressed on myeloid cells) are provided. Specifically, two (2) members of TREMs, TREM-1 and TREM-2 are disclosed. TREM-1 is a transmembrane glycoprotein expressed selectively on blood neutrophils and a subset of monocytes but not on lymphocytes and other cell types and is upregulated by bacterial and fungal products. Use of TREM-1 in treatment and diagnosis of various inflammatory diseases is also provided. TREM-2 is also a transmembrane glycoprotein expressed selectively on mast cells and peripheral dendritic cells (DCs) but not on granulocytes or monocytes. DC stimulation via TREM-2 leads to DC maturation and resistance to apoptosis, and induces strong upregulation of CCR7 and subsequent chemotaxis toward macrophage inflammatory protein 3-beta. TREM-2 has utility in modulating host immune responses in various immune disorders, including autoimmune diseases and allergic disorders.

A method of manipulating allogeneic cells for use in allogeneic cell therapy protocols is described. The method provides a composition of highly activated allogeneic T-cells which are infused into immunocompetent cancer patients to elicit a novel anti-tumor immune mechanism called the “Mirror Effect”. In contrast to current allogeneic cell therapy protocols where T-cells in the graft mediate the beneficial graft vs. tumor (GVT) and detrimental graft vs. host (GVH) effects, the allogeneic cells of the present invention stimulate host T-cells to mediate the “mirror” of these effects. The mirror of the GVT effect is the host vs. tumor (HVT) effect. The “mirror” of the GVH effect is the host vs. graft (HVG) effect. The effectiveness and widespread application of the anti-tumor GVT effect is limited by the severe toxicity of the GVH effect. In the present invention, the anti-tumor HVT effect occurs in conjunction with a non-toxic HVG rejection effect. The highly activated allogeneic cells of the invention can be used to stimulate host immunity in a complete HLA mis-matched setting in patients that have not had a prior bone marrow transplant or received chemotherapy and / or radiation conditioning regimens.

Methods and devices for isolating and diagnosing disease with a cell adhesion matrix system, mimicking a metastatic, cardiovascular or placental environment, are disclosed. The cell adhesion matrix facilitates the enrichment of target cells such as metastatic tumor cells, fetal cells and endothelial progenitor cells from a fluid sample such as blood for diagnostic and therapeutic applications in treating patients afflicted with disease, such as cancerous, cardiovascular and fetal diseases, as well as for research applications in molecular analysis of metastatic, and cardiovascular and fetal diseases. Blood test prototypes and methods for the cell enrichment and detection of circulating tumor and endothelial cells using multiplex molecular analysis are described herein. In addition, methods and compositions for determining host immunity to tumor in subjects with risk of cancer progression and methods for isolating an enriched fraction of fetal cells from pregnant females for prenatal diagnosis are also described herein.

Disclosed herein are compositions and methods for eliciting immune responses against antigens. In particular embodiments, the compounds and methods elicit immune responses against antigens that are otherwise recognized by the host as “self” antigens. The immune response is enhanced by presenting the host immune system with a chimeric antigen comprising an immune response domain and a target binding domain, wherein the target binding domain comprises a xenotypic antibody fragment. By virtue of the target binding domain, antigen presenting cells take up, process, and present the chimeric antigen, eliciting both a humoral and cellular immune response.

The present invention pertains to engineered T-cells, method for their preparation and their use as medicament, particularly for immunotherapy. The engineered T-cells of the invention are characterized in that the expression of beta 2-microglobulin (B2M) and / or class II major histocompatibility complex transactivator (CIITA) is inhibited, e.g., by using rare-cutting endonucleases able to selectively inactivating by DNA cleavage the gene encoding B2M and / or CIITA, or by using nucleic acid molecules which inhibit the expression of B2M and / or CIITA. In order to further render the T-cell non-alloreactive, at least one gene encoding a component of the T-cell receptor is inactivated, e.g., by using a rare-cutting endonucleases able to selectively inactivating by DNA cleavage the gene encoding said TCR component. In addition, expression of immunosuppressive polypeptide can be performed on those modified T-cells in order to prolong the survival of these modified T cells in host organism. Such modified T-cell is particularly suitable for allogeneic transplantations, especially because it reduces both the risk of rejection by the host's immune system and the risk of developing graft versus host disease. The invention opens the way to standard and affordable adoptive immunotherapy strategies using T-Cells for treating cancer, infections and auto-immune diseases.

Disclosed herein are compositions and methods for eliciting immune responses against antigens. In particular, the compounds and methods elicit immune responses against foreign antigens that are otherwise recognized by the host as "self" antigens, thus breaking host tolerance to those antigens. Presenting the host immune system with a chimeric antigen comprising an immune response domain and a target binding domain, wherein the target binding domain comprises an antibody fragment, enhances the immune response against the foreign or tolerated antigen. Antigen presenting cells take up, process, and present the chimeric antigen, eliciting both a humoral and cellular immune response against the desired antigen.

The present invention includes compositions, systems and methods for the early detection and consistent determination of the extent, type and nature of a host immune response and the nature of the infectious disease using gene expression data.

The invention provides compositions and methods for treating ovarian cancer. Specifically, the invention relates to administering a genetically modified T cell having alpha-folate receptor (FR-alpha) binding domain and CD27 costimulatory domain to treat ovarian cancer. In an embodiment, the FR-alpha binding domain is fully human, thereby preventing a host immune response.

Disclosed are methods for treating cancer comprising administering a xenotypic antibody and a chemotherapeutic drug to a patient suffering from cancer. Also disclosed is a method for inducing a host immune response in a patient against a multi-epitopic in vivo tumor antigen present in the host serum, which antigen does not elicit an effective host immune response, comprising administering to the patient a chemotherapeutic drug and a composition comprising a binding agent that specifically binds to a first epitope on the antigen and allowing the binding agent to form a binding agent / antigen pair, wherein an effective host immune response is elicited against a second epitope on the antigen.

The present invention provides methods and compositions for the stimulation of immune responses. In particular, the present invention provides nanoemulsion compositions and methods of using the same for the induction of immune responses (e.g., innate and adaptive immune responses (e.g., for generation of host immunity against an environmental pathogen)). Compositions and methods of the present invention find use in, among other things, clinical (e.g. therapeutic and preventative medicine (e.g., vaccination)) and research applications.

A therapeutic reagent to control one or more reactions of the immune system in a host, or to deliver anti-tumour agents, or disease treatment agents to the host. The therapeutic reagent comprises a regulatory moiety and a carrier protein that inactivates or substantially reduces the activity of the regulatory moiety. Also, the therapeutic reagent includes a cleavage site at which cleavage of the therapeutic reagent can occur to free the regulatory moiety from the carrier protein so that the therapeutic reagent can act at a diseased site in the host.

The present invention relates to oncolytic vaccinia viruses which have been modified to promote anti-tumor immunity and / or reduce host immunity and / or antibody response against the virus. It is based, at least in part, on the discovery that oncolytic vaccinia virus (i) bearing a genome deletion of a gene that reduces T cell immunity (interleukin-18 binding protein); (ii) treated with a sialidase enzyme which is believed to reduce TLR2 activation and therefore the antibody response; (iii) carrying a gene that enhances cytotoxic T lymphocyte induction (e.g., TRIF) and / or (iv) reduces tumor myeloid-derived suppressor cells by reducing prostaglandin E2 reduces tumor growth. Accordingly, the present invention provides for immunooncolytic vaccinia viruses and methods of using them in the treatment of cancers.

The present invention is directed to compositions and methods for the treatment of diseases comprising the administration of compositions comprising one or more peptide(s) having a stimulatory effect on the afflicted host's immune system. Specifically, the invention relates to methods comprising the use of cationic amphipathic peptides having an alpha-helical structure and effecting activation of macrophages when administered in a therapeutically sufficient amount. The methods of the present invention are useful for the treatment of, for example, infectious diseases or cancer.

This invention provides a composition comprising an effective amount of glucan capable of enhancing efficacy of antibodies. This invention further provides the above compositions and a pharmaceutically acceptable carrier. This invention also provides a method for treating a subject with cancer comprising administrating the above-described composition to the subject. This invention provides a composition comprising effective amount of glucan capable of enhancing efficacy of vaccines. This invention also provides a method of treating a subject comprising administrating the above pharmaceutical composition to the subject. This invention provides a composition comprising effective amount of glucan capable of enhancing efficacy of natural antibodies. This invention provides a composition comprising effective amount of glucan capable of enhancing host immunity. This invention also provides a composition comprising effective amount of glucan capable of enhancing the action of an agent in preventing tissue rejection.

The present invention provides compositions and methods for specifically inhibiting host immune responses against expression vectors and target cells transfected with such vectors. In particular, methods of specifically inhibiting the humoral and cellular components of the host immune response to vector-associated antigens and target-cell associated antigens are described.

This invention provides methods and compositions for treating tumors. The cell population is made up of alloactivated lymphocytes from the patient or from one or more third-party donors that are alloactivated in a mixed lymphocyte culture. It can be placed into the tumor bed, or combined with tumor-associated antigen for administration to a distal site as a vaccine. The compositions recruit activated participation of the host Immune system, which then reacts against the tumor and provides a level of ongoing protection. Employing multiple third party donor cells confers particular advantages in terms of effectiveness, timing, and ease of use.

The present invention pertains to engineered immortalized T-cell lines, method for their preparation and their use as medicament, particularly for immunotherapy. The engineered immortalized T-cell lines of the invention are characterized in that the expression of endogenous T-cell receptors (TCRs) and beta 2-microglobulin (B2M) is inhibited, e.g., by using an endonuclease able to selectively inactivate the TCR and B2M genes in order to render the immortalized T-cells non-alloreactive. In addition, expression of immunosuppressive polypeptide can be performed on those engineered immortalized T-cells in order to prolong the survival of these T-cells in host organisms. Such engineered immortalized T-cells are particularly suitable for allogeneic transplantations, especially because it reduces both the risk of rejection by the host's immune system and the risk of developing graft versus host disease. The invention opens the way to standard and affordable adoptive immunotherapy strategies using immortalized T-cells for treating cancer, infections and auto-immune diseases.

The invention discloses an O type foot-and-mouth disease virus variant as well as a coding gene and application thereof. In the invention, an O type foot-and-mouth disease virus pan-Asia strain O / YS / CHA / 05 is firstly separated out, the nucleotide sequence of the O type foot-and-mouth disease virus pan-Asia strain O / YS / CHA / 05 SEQ ID NO: 1, and the amino acid sequence is SEQ ID NO: 2. In comparison with a VP1 amino acid sequence, the virus strain has 7 variable sites, five of which are centralized in a G-H ring. Mutation of the sites ensures that the virus variant has the capability of escaping from host immunity so as to have the superiority for becoming a popular virus strain. Therefore, the variant can be employed to prepare an inactivated vaccine for prevention and treatment of the variant and relevant strains, dominant antigen epitope of the variant can be employed to prepare a synthetic peptide vaccine, and the variant can be employed to develop novel O type foot-and-mouth disease virus vaccines such as VLP vaccine and the like. Therefore, the invention has important value in controlling the popularity of O / YS / CHA / 05 and relevant variable strains.

The present invention provides methods and compositions for the stimulation of immune responses. In particular, the present invention provides immunogenic nanoemulsion compositions and methods of using the same for the induction of immune responses (e.g., innate and / or adaptive immune responses (e.g., for generation of host immunity against a bacterial species of the genus Streptococcus (e.g., Streptococcus pneumoniae))). Compositions and methods of the present invention find use in, among other things, clinical (e.g. therapeutic and preventative medicine (e.g., vaccination)) and research applications.

The present invention provides methods and compositions for the stimulation of immune responses. In particular, the present invention provides nanoemulsion compositions and methods of using the same for the induction of immune responses (e.g., innate and adaptive immune responses (e.g., for generation of host immunity against an environmental pathogen)). Compositions and methods of the present invention find use in, among other things, clinical (e.g. therapeutic and preventative medicine (e.g., vaccination)) and research applications.

The invention provides therapeutics and methods to induce a mammalian host, including a human, to produce antibodies, which agonize death receptors and cause the apoptotic death of target cells within the host's body. The therapeutics are vaccine compositions, including genetic vaccines encoding death receptor antigens of the tumor necrosis factor receptor family. Also provided are means and methods for overcoming host immunological tolerance to death receptors. The vaccines are useful against cancer cells and other death receptor bearing target cells within the host, and can be used in both therapeutic and prophylactic settings. The vaccines are also useful for diagnostic testing of the immunocompetence of a host.

The present invention provides methods and compositions for the stimulation of immune responses. Specifically, the present invention provides nanoemulsion compositions harboring one or more immunogens within the oil phase of the nanoemulsion and methods of using the same for the induction of immune responses (e.g., innate and / or adaptive immune responses (e.g., for generation of host immunity against an environmental pathogen)). Compositions and methods of the invention find use in, among other things, clinical (e.g., therapeutic and preventative medicine (e.g., vaccination)) and research applications.

The present invention is directed to compositions and methods for the treatment of diseases comprising the administration of compositions comprising one or more peptide(s) having a stimulatory effect on the afflicted host's immune system. Specifically, the invention relates to methods comprising the use of cationic amphipathic peptides having an alpha-helical structure and effecting activation of macrophages when administered in a therapeutically sufficient amount. The methods of the present invention are useful for the treatment of, for example, infectious or cancer.

A method of manipulating allogeneic cells for use in allogeneic cell therapy protocols is described. The method provides a composition of highly activated allogeneic T-cells which are infused into immunocompetent cancer patients to elicit a novel anti-tumor immune mechanism called the “Mirror Effect”. In contrast to current allogeneic cell therapy protocols where T-cells in the graft mediate the beneficial graft vs. tumor (GVT) and detrimental graft vs. host (GVH) effects, the allogeneic cells of the present invention stimulate host T-cells to mediate the “mirror” of these effects. The mirror of the GVT effect is the host vs. tumor (HVT) effect. The “mirror” of the GVH effect is the host vs. graft (HVG) effect. The effectiveness and widespread application of the anti-tumor GVT effect is limited by the severe toxicity of the GVH effect. In the present invention, the anti-tumor HVT effect occurs in conjunction with a non-toxic HVG rejection effect. The highly activated allogeneic cells of the invention can be used to stimulate host immunity in a complete HLA mis-matched setting in patients that have not had a prior bone marrow transplant or received chemotherapy and / or radiation conditioning regimens.

A method for inhibiting rejection of tissues transplanted into a mammalian host is disclosed. Treatment of the tissues with an enzyme or combination of enzyme, particularly papain, to eliminate cell surface structures necessary for recognition by the host's immune system, particularly MHC Class I molecules, avoids or reduces the attack of the host's immune system on the transplanted tissues. Tissues that are enzymatically shaved of MHC Class I antigens and / or other critical adhesion molecules can be rendered at least temporarily resistant or immune to attack by cytolytic T lymphocytes, helper T lymphocytes, antibodies, or other effector cells of a host's immune system, thereby enhancing the survivability of the tissues in the host after transplant.

The invention relates to improvements relating to cancer therapy based on the identification of a number of regions of CPG2 which contain epitopes which appear to be involved in the production of a host immune response and which may be modified to alter the immunogenicity in patients. Production of fusions of CPG2 with an antibody, where the CPG2 protein has been tagged provides a CPG2 protein which has reduced immunogenicity. By using partially glycosylated enzyme obtainable by P. pastoris expression, the efficacy of antibody-CPG2 fusions is enhanced.

The invention discloses a microbial feed additive capable of enhancing immunity of fish and an application of the feed additive. The microbial feed additive includes, by weight, 16-22 parts of fructus forsythiae, 16-19 parts of herba andrographitis, 12-17 parts of artemisia apiacea, 15-21 parts of Chinese rhubarb, 1-2 parts of angelica sinensis, 13-20 parts of houttuynia cordata, 10-15 parts of radix glycyrrhizae, 7-11 parts of acanthopanax roots, 0.6-0.9 parts of garlic, 2-3 parts of pericarpium citri reticulatae, 3-5 parts of eucommia ulmoides, 0.8-1.3 parts of bacillus subtilis, and 1-1.4 parts of lactobacillus plantarum. The microbial feed additive is free of toxic and side effects, has no pollution and residual, is free of generating drug resistance, can promote secretion of antibodies by a host, improves activity of immune cells of the host and improves immunity and resistance of body. The microbial feed additive also maintains microecological balance in intestinal tracts and best immune state, and also improves digestion and absorption rate of nutrients.