Abstract: The invention provides a method for the expansion of anti-tumor T-cells, comprising the steps of: a) providing a phagocytosable particle, having one or more tumor neoantigenic constructs tightly associated thereto, wherein the tumor neoantigenic construct comprises an amino-acid sequence comprising at least one mutated amino acid known or suspected to be associated with a cancer in a subject, or a mutated or non-mutated amino-acid sequence known or suspected to be expressed in a cancer cell in the subject; b) providing a viable antigen-presenting cell; c) contacting the particle with the antigen-presenting cell in vitro under conditions allowing phagocytosis of the particle by the antigen-presenting cell; d) providing a T-cell sample comprising viable T-cells from the subject; e) contacting the T-cell sample with the antigen-presenting cell contacted with the particle in vitrounder conditions allowing specific activation of anti-tumor T-cells in response to antigen presented by the antigen-presenting cell.

Abstract: The present invention provides a method for diagnosing and monitoring MS on the basis of an immunoassay using MSBI1.176 or MSBI2.176 Rep protein or fragments thereof as an antigen for binding antibodies against MSBI1.176 or MSBI2.176 Rep protein from a subject's sample.

Abstract: Described herein are tolerogenic compositions for use in a method of treatment for multiple sclerosis (MS) in a MS subject exhibiting T-cell autoreactivity against an endogenous epitope corresponding to a T-cell epitope comprising a sequence of at least 8 consecutive amino acid residues differing from a sub-sequence of SEQ ID NO: 5 by 0-2 residue substitutions, deletions and/or insertions, or the composition comprising a nucleic acid encoding said therapeutic T-cell epitope. Also described are methods for determining antigen-specific T-cell activation in a test subject, comprising providing a test sample derived from the test subject comprising viable T-cells; determining antigen-specific activation of the T-cells of the test sample in vitro in response to a test antigen comprising a T-cell epitope; and comparing the determined antigen-specific activation to a relevant reference to determine the degree of MS-related autoimmunity in the test subject.

Abstract: The present invention provides an in vitro method for the manufacture of a dendritic cell (DC) cancer vaccine, said method comprising the steps of: (i) providing a plurality of phagocytosable particles, wherein each phagocytosable particle comprises a core and an antigenic construct tightly associated to the core, wherein the antigenic construct comprises at least one epitope peptide having an amino acid sequence corresponding to an amino acid sequence of a part of a protein or peptide known or suspected to be expressed by a cancer cell in a subject; (ii) providing a sample of DCs; and (iii) contacting the sample of DCs with the plurality of phagocytosable particles in vitro and under conditions allowing for the phagocytosis of at least one phagocytosable particle by a DC. The present invention also provides a DC cancer vaccine produced by the method of the invention, and the use a DC cancer vaccine of the invention as a medicament and for the ex vivo expansion of anticancer T-cells.

Abstract: Methods for assaying antigen-specific T-cell activation in vitro, comprising the steps of (a) providing a phagocytable particle, having a candidate antigen polypeptide tightly associated thereto, wherein the particle with the associated polypeptide has been subjected to a denaturing wash resulting in an endotoxin level low enough to not interfere with the subsequent steps; (b) providing a viable antigen-presenting cell; (c) contacting the washed particle with the antigen-presenting cell under conditions allowing phagocytosis of the particle by the antigen-presenting cell; (d) providing a T-cell sample to be assayed comprising viable T-cells; (e) contacting the T-cell sample with the antigen-presenting cell contacted with the particle under conditions allowing specific activation of T-cells in response to an antigen presented by an antigen-presenting cell; and (f) determining the degree of T-cell activation in the T-cell sample.

Abstract: The present invention provides a method for the expansion of HPV immunogen specific T cells, comprising the steps of: i. providing a phagocytosable particle comprising a core and a human papillomavirus (HPV) immunogen tightly associated to the core; wherein the HPV immunogen has an amino acid sequence that corresponds to the amino acid sequence of a HPV protein, or has an amino acid sequence that corresponds to an amino acid sequence of a part of a HPV protein; ii. providing APCs; iii. contacting the phagocytosable particle comprising a core and a HPV immunogen with the APCs from step ii in vitro, and under conditions allowing phagocytosis of the HPV immunogen by the APCs; iv. providing T-cells that have been harvested from a subject; v. contacting the T-cells with the APCs from step iii) in vitro, and under conditions allowing specific activation of HPV immunogen specific T-cells.

Abstract: Methods for assaying antigen-specific T-cell activation in vitro, comprising the steps of (a) providing a phagocytable particle, having a candidate antigen polypeptide tightly associated thereto, wherein the particle with the associated polypeptide has been subjected to a denaturing wash resulting in an endotoxin level low enough to not interfere with the subsequent steps; (b) providing a viable antigen-presenting cell; (c) contacting the washed particle with the antigen-presenting cell under conditions allowing phagocytosis of the particle by the antigen-presenting cell; (d) providing a T-cell sample to be assayed comprising viable T-cells; (e) contacting the T-cell sample with the antigen-presenting cell contacted with the particle under conditions allowing specific activation of T-cells in response to an antigen presented by an antigen-presenting cell; and (f) determining the degree of T-cell activation in the T-cell sample.

Abstract: The invention provides a phagocytosable particle for use in the treatment or prophylaxis of cancer in a subject, wherein the phagocytosable particle comprises a core and a neoantigenic construct tightly associated to the core, and wherein the neoantigenic construct comprises a neoepitope peptide having an amino acid sequence corresponding to an amino acid sequence of a part of a protein or peptide known or suspected to be expressed by a cancer cell in the subject, wherein the part of the protein or peptide has at least one somatic mutated amino acid. The invention also relates to injectable pharmaceutical compositions for use in the treatment or prophylaxis of cancer.

Abstract: A tolerogenic composition for use in a method of treatment for multiple sclerosis (MS) in a MS patient exhibiting T-cell autoreactivity against an endogenous epitope corresponding to a T-cell epitope comprised in the amino-acid sequence of SEQ ID NO: 5, the composition comprising a therapeutic T-cell epitope comprising a sequence of 8 consecutive amino acid residues differing from a sub-sequence of SEQ ID NO: 5 by 0-2 residue substitutions, deletions and/or insertions, or the composition comprising a nucleic acid encoding said therapeutic T-cell epitope.

Abstract: Methods for assaying antigen-specific T-cell activation in vitro, comprising the steps of (a) providing a phagocytable particle, having a candidate antigen polypeptide tightly associated thereto, wherein the particle with the associated polypeptide has been subjected to a denaturing wash resulting in an endotoxin level low enough to not interfere with the subsequent steps; (b) providing a viable antigen-presenting cell; (c) contacting the washed particle with the antigen-presenting cell under conditions allowing phagocytosis of the particle by the antigen-presenting cell; (d) providing a T-cell sample to be assayed comprising viable T-cells; (e) contacting the T-cell sample with the antigen-presenting cell contacted with the particle under conditions allowing specific activation of T-cells in response to an antigen presented by an antigen-presenting cell; and (f) determining the degree of T-cell activation in the T-cell sample.

Abstract: The invention provides a method for the expansion of anti-tumor T-cells, comprising the steps of: a) providing a phagocytosable particle, having one or more tumor neoantigenic constructs tightly associated thereto, wherein the tumor neoantigenic construct comprises an amino-acid sequence comprising at least one mutated amino acid known or suspected to be associated with a cancer in a subject, or a mutated or non-mutated amino-acid sequence known or suspected to be expressed in a cancer cell in the subject; b) providing a viable antigen-presenting cell; c) contacting the particle with the antigen-presenting cell in vitro under conditions allowing phagocytosis of the particle by the antigen-presenting cell; d) providing a T-cell sample comprising viable T-cells from the subject; e) contacting the T-cell sample with the antigen-presenting cell contacted with the particle in vitrounder conditions allowing specific activation of anti-tumor T-cells in response to antigen presented by the antigen-presenting cell.

Abstract: Dander from the domestic cat (Felis domesticus) is one of the most common causes of IgE mediated allergy. The present invention relates to a recombinant folded Fel d 1 with molecular and biological properties similar to the natural counterpart and specifically a synthetic gene coding for a direct fusion of Fel d 1 chain 2 N-terminally to chain 1. E coli expression resulted in a non-covalently associated homodimer with an apparent molecular weight of 30 kDa defined by size exclusion chromatography, each 19177 Da subunit displayed a disulfide pattern identical to that found in the natural Fel d 1, and having identical fold of natural and recombinant Fel d 1. The, recombinant Fel d 1 provides for diagnosis and allergen specific immunotherapy of cat allergy.

Abstract: The present invention relates to a hypoallergenic protein consisting of at least one hypoallergenic molecule derived from an allergen, which is fused or conjugated to at least one second non-allergenic protein or fragment thereof.

Abstract: The present invention relates to a hypoallergenic protein consisting of at least one hypoallergenic molecule derived from an allergen, which is fused or conjugated to at least one second non-allergenic protein or fragment thereof.

Abstract: Methods for desensitization of a mammal suffering from IgE mediated allergy comprise the steps of: administering to said mammal a therapeutically effective amount of an immunogenic and hypoallergenic composition which comprises (i) a Phl p 6 molecule having an N-terminal truncation which makes the molecule at least lack IgE binding capacity, and/or (ii) a Phl p 6 molecule having a C-terminal truncation which makes the molecule at least lack IgE binding capacity, wherein the molecules of (i) and (ii), if employed in combination, together span the complete sequence of Phl p 6, and a pharmaceutically acceptable carrier.

Abstract: Low levels of antibodies reactive with a PAF-conjugate are related to an increased risk of developing cardiovascular diseases. Thus, compositions and methods of diagnosis and therapy for cardiovascular diseases are provided.

Abstract: The present invention relates to a hypoallergenic protein consisting of at least one hypoallergenic molecule derived from an allergen, which is fused or conjugated to at least one second non-allergenic protein or fragment thereof.

Abstract: Dander from the domestic cat (Felis domesticus) is one of the most common causes of IgE mediated allergy. The present invention relates to a recombinant folded Fel d 1 with molecular and biological properties similar to the natural counterpart and specifically a synthetic gene coding for a direct fusion of Fel d 1 chain 2 N-terminally to chain 1. E coli expression resulted in a non-covalently associated homodimer with an apparent molecular weight of 30 kDa defined by size exclusion chromatography, each 19177 Da subunit displayed a disulfide pattern identical to that found in the natural Fel d 1, and having identical fold of natural and recombinant Fel d 1. The, recombinant Fel d 1 provides for diagnosis and allergen specific immunotherapy of cat allergy.

Abstract: The invention relates to a hypoallergenic immunogenic molecule derived from the Phl p 6 allergen, wherein the Phl p6 molecule has an N-terminal and/or C-terminal deletion which makes the molecule at least substantially lack IgE binding capacity. The invention also relates to a hypoallergenic immunogenic combination of molecules derived from the Phl p 6 allergen, comprising (i) a Phl p 6 molecule having an N-terminal deletion which makes the molecule at least substantially lack IgE binding capacity, and (ii) a Phl p 6 molecule having a C-terminal deletion which makes the molecule at least substantially lack IgE binding capacity, which two molecules together encompass the complete sequence of Phl p 6. The invention further relates to the use of the hypoallergenic immunogenic molecule or molecule mixture in hyposensitization and diagnosis.

Abstract: The present invention relates to a novel drug candidate having a potential for universal therapy of allergy and asthma. The invention provides a Fab (antibody fragment), having the following characteristics: a) inhibits the IgE-Fc?RI interaction; b) binds to free and cell-bound IgE; and c) is non-anaphylactic.