Abstract: Methods and processes for the purification of PRAME are provided. In particular, methods for reducing the aggregation of PRAME during a diluent exchange from diluent A to diluent B comprising: (i) adding a polyanionic compound to diluent A prior to or contemporaneously with the exchange; and (ii) exchanging protein from diluent A to diluent B are provided. Compositions produced by the method are also provided.

Abstract: The invention provides compositions comprising liposomes, an antigen capable of inducing a humoral immune response, a carrier comprising a continuous phase of a hydrophobic substance, and an adjuvant that activates or increases the activity of TLR2. The invention also provides uses for such compositions in inducing a humoral response and methods for their use in the treatment of a disease, disorder or ailment ameliorated by a humoral immune response.

Abstract: A pharmaceutical formulation comprises a plurality of seamless minicapsules having a diameter from 0.5 mm to 5 mm, at least some of the minicapsules containing a methyxanthine as one active ingredient, and at least some of the minicapsules containing a corticosteroid as another active ingredient.

Abstract: The present invention provides a vaccine composition which comprises a cellular immunity induction promoter universally usable against various antigens in cellular immunity induction by mucosal administration of the antigen and exerts a high cellular immunity inducing effect by mucosal administration. The present invention provides a vaccine composition for mucosal administration to induce cellular immunity, comprising: (i) an antigen; and (ii) one or more cellular immunity induction promoters selected from the group consisting of a TLR ligand, a cyclic dinucleotide, a helper peptide and an immunomodulatory small molecule drug.

Abstract: Provided are compositions and methods useful for modulation of signaling through the Toll-like receptors TLR7 and/or TLR8. The compositions and methods have use in treating or preventing disease, including cancer, autoimmune disease, infectious disease, inflammatory disorder, graft rejection, and graft-verses-host disease.

Abstract: The present invention relates to the use of a milled homogenate and/or a suspension and/or a cell lysate, stemming from a tumor resistant to at least one anti-tumoral compound in order to immunize and generate in vitro an antibody, or one of its functional fragments, directed against a tumoral antigen specifically expressed at the surface of said resistant tumor and being possibly involved in the resistance of said resistant tumor. More particularly, the present invention is directed to such antibodies obtained by applying the method, such as the antibodies 1A6, 1A9, 2E11, 3C11 and 3G7, as well as to their use for treating cancer.

Abstract: The invention relates to a method of therapy against tumors and their metastases, which preferentially settle in bone tissue, comprising administering to a patient in need thereof an active ingredient which comprises at least one binding molecule that binds to human bone sialoprotein or a fragment thereof.

Abstract: The invention provides polymer compositions for cell and drug delivery.

Abstract: AnnexinA2 (ANXA2), a member of the Annexin family of calcium-dependent, phospholipid binding proteins, is one of a panel of identified antigens recognized by the post-vaccination sera of patients who demonstrated prolonged disease-free survival following multiple vaccinations. AnnexinA2 is abundantly expressed in pancreatic adenocarcinomas and cell surface/membrane AnnexinA2 increases with the progression from premalignant lesions to invasive pancreatic adenocarcinomas. The cytoplasmic to cell surface translocation of AnnexinA2 expression is critical for pancreatic cancer cell invasion. In addition, phosphorylation of AnnexinA2 at Tyrosine 23 is important for its localization to the cell surface and for the invasion of pancreatic cancer cells. Finally, loss of AnnexinA2 leads to the loss of the Epithelial-Mesenchymal Transition.

Abstract: Compositions suitable for use as adjuvants in the preparation of vaccines, particularly those vaccines useful in the treatment of cancer, are provided. Methods for inhibiting tumor growth in an animal are also disclosed. Methods for immunizing an animal against cancer, such as prostate cancer, are also described. The adjuvants described are comprised of an extracellular matrix material, such as small intestinal submucosal (SIS) tissue. The preparations may take the form of sheets, gels, liquids (injectable), trocar, or other solid or semi-solid preparation. The invention provides for enhanced tumor inhibition of 2-fold or greater, compared to vaccine preparations without the extracellular matrix material, or from 4- to 5-fold, compared to preparations without the adjuvant promoting extracellular materials.

Abstract: Peptides including an amino acid sequence of a fragment of mammalian Toll-like receptor-4 (TLR-4), analogs and derivatives thereof, and pharmaceutical compositions including these peptides. Methods for modulating a TLR-4 mediated immune response, particularly stimulating TLR-4 mediated immune response, thereby treating infectious diseases and cancer.

Abstract: The present invention provides a cancer vaccine composition for mucosal administration comprising (i) a HER2/neu E75 peptide and/or a modified HER2/neu E75 peptide; and (ii) a first cellular immunity induction promoter.

Abstract: Disclosed is a vaccine composition for transdermal administration to induce cellular immunity, comprising an antigen, wherein Th1 cell ratio in a model animal for immunological evaluation that received the composition is 10% or more.

Abstract: Provided are antigenic determinants of human death receptor DR5. The antigenic determinants have the amino acid sequence of LITQQDLAPQQRA (SEQ ID No. 7), wherein the core polypeptide is QDLAP (SEQ ID No. 1). The polypeptides comprising said antigenic determinants can activate the signal pathway downstream of DR5 after binding to monoclonal antibody AD5-10, then result in apoptosis. The antigenic determinants can be used for screening and preparing anti-human DR5 agonistic antibody, small molecular compound binding to DR5 and DR5 vaccine.

Abstract: The present invention relates to PRAME specific primers and probes, diagnostic kits and methods. The invention further relates to treatment of specific populations of cancer patients suffering from PRAME expressing tumours.

Abstract: It is an object of the present invention to provide novel and highly active cyclic-di-nucleotide (CDN) immune stimulators that activates DCs via a recently discovered cytoplasmic receptor known as STING (Stimulator of Interferon Genes). In particular, the CDNs of the present invention are provided in the form of a composition comprising one or more cyclic purine dinucleotides that induce STING-dependent TBK1 activation, wherein the cyclic purine dinuclotides present in the composition are substantially pure Rp,Rp or Rp,Sp stereoisomers, and particularly substantially pure Rp,Rp, or RpSp CDN thiophosphate diastereomers.

Abstract: Pharmaceutical compositions comprising molecules produced by antigen-stimulated peripheral blood mononuclear cells (PBMCs) that induce systemic immune responses to cancers are encompassed herein, as are methods for making and administering such molecules and pharmaceutical compositions comprising same. Also encompassed herein are mixtures of molecules produced by antigen-stimulated PBMCs and compositions thereof for use in treating cancer. Methods for stimulating a systemic immune response in a subject afflicted with a cancer are also envisioned, whereby molecules produced by antigen-stimulated PBMCs or supernatants comprising same are administered to the subject, wherein the molecules stimulate an immune response to the cancer in the subject.

Abstract: 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.

Abstract: Therapeutic methods and vaccinia virus therefor are provided. The viruses are designed so that they accumulate in immunoprivileged tissues and cells, such as in tumors and other proliferating tissue and in inflamed tissues, compared to other tissues, cells and organs, so that they exhibit relatively low toxicity to host organisms. Combinations of the viruses and anti-cancer agents and uses thereof for treating cancer also are provided.

Abstract: Using phosphoproteomics, we profiled the phosphorylation levels of hundreds of proteins concurrently across an isogenic model of breast cancer metastasis. Among them is TRPV4, a calcium channel that we found to be overexpressed in invasive breast tumors compared to ductal carcinoma in situ, a pre-neoplastic lesion and normal tissues. TRPV4 was also found to be elevated mostly in invasive breast cancer cell lines and less so in non-invasive breast cancer cell lines. These data led us to hypothesize that TRPV4 confer early traits of metastatic cancer cells. Functional studies revealed that silencing of TRPV4 expression diminished breast cancer cell migration and invasion significantly but not proliferation. Silencing expression of TRPV4 in metastatic breast cancer cells also reduced the number and size of metastatic colonies in mice. This supports the notion that TRPV4 is an attractive drug target to curb metastasis.

Abstract: Streptavidin(SA)-4-1BBL and TLR agonists such as monophosphoryl lipid A (MPL) exhibit surprising synergy as adjuvants, inducing immune responses against weak antigens. Accordingly, there are provided adjuvant compositions comprising 4-1BBL and a toll-like receptor (TLR) agonist, such as MPL, methods of inducing an immune response against an antigen in a subject, comprising administering to the subject (a) the antigen, (b) a TLR agonist and, (c) 4-1BBL, and methods of treating a tumor or a cancer in a subject, comprising administering to the subject (a) an antigen associated with the tumor or cancer, (b) a TLR agonist, and (c) 4-1BBL.

Abstract: The present invention provides a dendritic cell-based vaccine by fusing a canine tumor cell and an allogeneic dendritic cell, and a method for preparing the same. The fusion cells expressing canine tumor antigens are generated by fusing canine bone marrow-derived dendritic cells and canine tumor cells. The canine immune system can be induced to produce tumor specific T lymphocytes and natural killer cells when the fusion cells used as a vaccine is injected into a canine body.

Abstract: Compositions suitable for use as adjuvants in the preparation of vaccines, particularly those vaccines useful in the treatment of cancer, are provided. Methods for inhibiting tumor growth in an animal are also disclosed. Methods for immunizing an animal against cancer, such as prostate cancer, are also described. The adjuvants described are comprised of an extracellular matrix material, such as small intestinal submucosal (SIS) tissue. The preparations may take the form of sheets, gels, liquids (injectable), trocar, or other solid or semi-solid preparation. The invention provides for enhanced tumor inhibition of 2-fold or greater, compared to vaccine preparations without the extracellular matrix material, or from 4- to 5-fold, compared to preparations without the adjuvant promoting extracellular materials.

Abstract: Disclosed are mammalian tumor and/or cancer cell conditioned substrate preparations having tumor inhibiting activity. In some embodiments, the mammalian tumor and/or cancer cell conditioned substrate preparations are essentially free of cellular components. These preparations comprise a conditioned heterologous acellular collagenous tissue preparation, and may be prepared using a mammalian extracellular matrix substrate. The conditioned substrates include many different anti-tumor and/or anti-cancer biomolecules, such as that population of anti-tumor biomolecules that are secreted and/or produced by mammalian tumor and/or cancer cells as they grow on a substrate, thus imparting the anti-tumor and/or anti-cancer properties to the conditioned substrates of the invention. The present disclosure also provides methods for preparing the mammalian tumor and/or cancer cell conditioned substrates, as well as methods for using the preparations to inhibit tumor growth, such as in a vaccine or wound dressing.

Abstract: Compositions and methods for delivering tumor associated antigens and immune modulatory molecules to result in a therapeutic effect are disclosed. The compositions and methods use stably integrating lentiviral delivery systems. The methods are useful for therapeutically and prophylactically treating cancer such as colon cancer.

Abstract: A vaccination method is provided. The method comprises administering to a mammal a histone deacytelase inhibitor in conjunction with a vaccine that expresses an antigen to which the mammal has a pre-existing immunity.

Abstract: Compositions and methods, including vaccines and pharmaceutical compositions for inducing or enhancing an immune response are disclosed based on the discovery of useful immunological adjuvant properties in a synthetic, glucopyranosyl lipid adjuvant (GLA) that is provided in substantially homogeneous form. Chemically defined, synthetic GLA offers a consistent vaccine component from lot to lot without the fluctuations in contaminants or activity that compromise natural-product adjuvants. Also provided are vaccines and pharmaceutical compositions that include GLA and one or more of an antigen, a Toll-like receptor (TLR) agonist, a co-adjuvant and a carrier such as a pharmaceutical carrier.

Abstract: The invention provides compositions and methods for utilizing scaffolds in cancer vaccines.

Abstract: Various embodiments of the invention provide methods of treating cancer. Many embodiments provide methods of treating cancer using stem cells. In one embodiment the method comprises removing cancer cells from a patient and culturing the cancer cells in the presence of stem cells under conditions such that the stem cells differentiate into stem cell-derived cancer cells (SCDCC) which can comprise stem cell derived non-invasive and/or invasive cancer cells. An amount of the SCDCC is introduced into the patient sufficient to induce the patient's immune system to produce antibodies which inhibit or destroy the patient's cancer cells. The SCDCC may also be genetically modified to produce various immune stimulating proteins which enhance the patient's immune response to the cancer cells and improves the efficacy of the SCDNIC in treating the patient's cancer.

Abstract: The present disclosure relates generally to the membrane transporter NaPi2b (SLC34A2) as a target for therapy, including immunotherapy, and particularly cancer therapy. The SLC34A2 epitope peptide encompassing amino acids 312-340 of SLC34A2 has been identified as an ovarian cancer epitope using the monoclonal antibody MX35. The invention also relates to the use of SLC34A2 and particularly SLC34A2 peptides in generating antibodies which have anti-tumor or anti-cancer activity or in stimulating an immunological response. The invention further relates to antibodies specifically directed against NaPi2b (SLC34A2) and the SLC34A2 peptide(s), including veneered, chimeric, single chain and humanized antibodies. Methods for generating an immune response and for treatment of tumors and cancer are also provided. Assays for screening and identifying compounds directed against SLC34A2, including the SLC34A2 epitope peptide, and additional antibodies are provided.

Abstract: A method for inhibiting growth and/or metastasis of a tumor in a mammal is disclosed. The method comprises administering to a mammal in need thereof an effective amount of stem cells comprising a transgene encoding at least one oncogenic protein, wherein the stem cells are immortal and show no signs of neoplastic transformation; and administering to the mammal a vaccine composition comprising an effective amount of at least one immunogenic protein capable of eliciting at least one antibody specific against the at least one oncogenic protein, and thereby inhibiting growth and/or metastasis of a tumor in the mammal. A therapeutic kit for inhibiting growth and/or metastasis of a tumor in a mammal is also disclosed.

Abstract: We demonstrate herein that neuritin controls the homeostasis of regulatory T cells in an antigen dependent manner. Based on this discovery, we describe herein the application of neuritin as a therapeutic agent to manipulate antigen specific regulatory T cells in various disease settings is described. Thus manipulation of Treg cells and DCs through neuritin can be used to enhance immunotherapy of autoimmune diseases, cancer and infectious diseases, as well as enhance lymphocyte engraftment in settings of donor lymphocyte infusion, bone marrow transplant, as well as other types of transplants, and adoptive transfer.

Abstract: Methods of treating, preventing and/or managing cancer as well as and diseases and disorders associated with, or characterized by, undesired angiogenesis are disclosed. Specific methods encompass the administration of an immunomodulatory compound alone or in combination with a second active ingredient. The invention further relates to methods of reducing or avoiding adverse side effects associated with chemotherapy, radiation therapy, hormonal therapy, biological therapy or immunotherapy which comprise the administration of an immunomodulatory compound. Pharmaceutical compositions, single unit dosage forms, and kits suitable for use in methods of the invention are also disclosed.

Abstract: Methods are disclosed for producing defective ribosomal products (DRiPs) in blebs (DRibbles) by contacting cells with a proteasome inhibitor, and in some examples also an autophagy inducer, thereby producing treated cells. DRibbles can be used to load antigen presenting cells (APCs), thereby allowing the APCs to present the DRiPs and antigenic fragments thereof. Immunogenic compositions that include treated cells, isolated DRibbles, or DRibble-loaded APCs are also disclosed. Methods are also provided for using treated cells, isolated DRibbles, or DRibble-loaded APCs to stimulate an immune response, for example in a subject. For example, DRibbles obtained from a tumor cell can be used to stimulate an immune response against the same type of tumor cells in the subject. In another example, DRibbles obtained from a pathogen-infected cell or cell engineered to express one or more antigens of a pathogen can be used to stimulate an immune response against the pathogen in the subject.

Abstract: The present invention relates to the provision of vaccines which are specific for a patient's tumor and are potentially useful for immunotherapy of the primary tumor as well as tumor metastases. In one aspect, the present invention relates to a method for providing an individualized cancer vaccine comprising the steps: (a) identifying cancer specific somatic mutations in a tumor specimen of a cancer patient to provide a cancer mutation signature of the patient; and (b) providing a vaccine featuring the cancer mutation signature obtained in step (a). In a further aspect, the present invention relates to vaccines which are obtainable by said method.

Abstract: Disclosed herein are compositions and methods useful for the treatment of cancer, such as breast cancer. In some embodiments, the methods and compositions include human prolactin, or human prolactin in conjunction with a cytotoxic agent. In other embodiments, the methods and compositions include one or more of human prolactin, growth hormone and placental lactogen, or one or more of human prolactin, growth hormone and placental lactogen in conjunction with a cytotoxic agent. In some embodiments, the cytotoxic agent comprises a chemotherapeutic agent.

Abstract: Methods are provided for treating a vaccine containing infectious particles which may be viral, bacterial, and/or cellular in nature. Preferred methods include the steps of adding an effective, non-toxic amount of an endogenous photosensitizer to the fluid and exposing the fluid to photoradiation sufficient to inactivate the infectious particles but not enough to damage the antigenic characteristics of the infectious particles.

Abstract: Disclosed are: a peptide comprising an amino acid sequence composed of contiguous nine amino acid residues derived from a WT1 protein, wherein an amino acid residue at position 2 in the amino acid sequence is selected from the group consisting of Ala, Ile, Leu, Val, Phe, Tyr, Ser and Asp and an amino acid residue at position 9 in the amino acid sequence is Arg; a polynucleotide encoding the peptide; a pharmaceutical composition comprising the peptide; and a method for the induction of a WT1-specific CTL using the peptide.

Abstract: Described is a vaccine for prevention and treatment of cancer characterized by microsatellite instability (MSI). The vaccine contains an MSI-specific frameshift peptide (FSP) generating humoral and cellular responses against tumor cells or a nucleic acid encoding said FSP. The vaccine of the present invention is particularly useful for the prevention/treatment of colorectal cancer, endometrial cancer, gastric cancer or small bowel cancer.

Abstract: The present invention relates to the use of compounds of formula (I) in the treatment of Epidermal Growth Factor Receptor (EGFR) family members dependent diseases or diseases that have acquired resistance to agents that target EGFR family members, use of said compounds for the manufacture of pharmaceutical compositions for the treatment of said diseases, combinations of said compounds with EGFR modulators for said use, methods of treating said diseases with said compounds and pharmaceutical preparations for the treatment of said diseases comprising said compounds alone or in combination, especially with an EGFR modulator.

Abstract: The invention relates to fusion constructs, methods of using fusion constructs and methods of treating undesirable or aberrant cell proliferation or hyperproliferative disorders, such as tumors, cancers, neoplasia and malignancies.

Abstract: A first composition comprising a ligand part being able to specifically bind to a target, the target being on a diseased cell of an organism, and an epitope part having a non-self epitope, or encoding a non-self epitope, the non-self epitope not naturally being encoded by the organism, wherein the target is internalized after forming a complex with the composition and the non-self epitope is presented on the cell surface of said diseased cell of an organism after internalization.

Abstract: The present invention relates to antigen-specific immune regulatory response. Methods for detecting an antigen-specific immune regulatory response, methods for selecting candidate vaccine recipients, and methods for improved vaccination strategies are presented.

Abstract: The invention provides a peptide comprising a human cytolytic T lymphocyte (CTL) epitope from the human tumor-associated antigen (TAA) New Gene Expressed in Prostate (NGEP), which can be used in vaccine prevention or therapy of prostate cancer, as well as a nucleic acid encoding the peptide, a vector comprising the nucleic acid, a cell comprising the peptide, nucleic acid, or vector, and compositions thereof.

Abstract: The invention relates to methods of diagnosis and prognosis of cancer, and in particular NSCLC, the methods comprising determining the expression level of one or more genes. In some embodiments the invention relates to prognosis of early stage NSCLC.

Abstract: The invention features methods of diagnosis by assessing B7-H1 expression in a tissue from a subject that has, or is suspected of having, cancer, methods of treatment with agents that interfere with B7-H1-receptor interaction, methods of selecting candidate subjects likely to benefit from cancer immunotherapy, and methods of inhibiting expression of B7-H1.

Abstract: Compositions and methods which inhibit the expression of the TMEM92 gene or which inhibits the function of die TMEM92 protein can be used for treating, diagnosing and monitoring disease, for example cancer.

Abstract: A method of treating cancer in an immune-privileged site of a subject in need thereof is provided. The method comprises systemically administering to an area outside the immune-privileged site of the subject, a therapeutically effective amount of naive, viable cells of a tumor of the subject, the tumor being in the immune-privileged site so as to generate an immune response in the subject, thereby treating the cancer in the immune-privileged site of the subject.

Abstract: An active polypeptide comprising the amino acid sequence of SEQ ID NO:4, having an anti-tumor activity, and compositions and methods including the active polypeptide.

Abstract: Embodiments of the invention relate generally to ex vivo methods of quantifying expression of leukocyte-function associated mRNAs and using the quantification to characterize an individual's potential responsiveness to cancer immunotherapy. Certain embodiments relate to methods to monitor the efficacy of ongoing cancer immunotherapy by evaluating expression of leukocyte-function associated mRNAs genes before and administration of an anti-cancer immunotherapy regimen.