Abstract: The present invention relates to a composition comprising an isolated CD4+ Treg cell population, wherein the Treg cells have signatures for i) identifying that the T-cells are CD4+ regulatory Tcells, ii) identifying that the Treg cells are tissue type tropic, i.e they can migrate to the diseased tissue, iii) optionally identifying that the Treg cells are tropic with respect to the diseased tissue, i.e. they are homing cells, iv) identifying that the Treg cells are emigrant cells, i.e. they originate from the target tissue, and v) optionally identifying that the Treg cells are retained in the target tissue and optionally one or more X-signatures and/or one or more Y-signatures and one ore more Z-signatures.

Abstract: The present invention relates to composition comprising an isolated CD8+ Treg cell population, wherein the Treg cells have signatures for i) identifying that the T-cells are CD8+ regulatory Tcells, ii) identifying that the Treg cells are tissue type tropic, i.e they can migrate to the diseased tissue, iii) optionally identifying that the Treg cells are tropic with respect to the diseased tissue, i.e. they are homing cells, iv) identifying that the Treg cells are emigrant cells, i.e. they originate from the target tissue, and v) optionally identifying that the Treg cells are capable of being retained in the target tissue and optionally one or more X-signatures and/or one or more Y-signatures.

Abstract: The present invention relates to composition comprising an isolated CD8+ Treg cell population, wherein the Treg cells have signatures for i) identifying that the T-cells are CD8+ regulatory Tcells, ii) identifying that the Treg cells are tissue type tropic, i.e they can migrate to the diseased tissue, iii) optionally identifying that the Treg cells are tropic with respect to the diseased tissue, i.e. they are homing cells, iv) identifying that the Treg cells are emigrant cells, i.e. they originate from the target tissue, and v) optionally identifying that the Treg cells are capable of being retained in the target tissue and optionally one or more X-signatures and/or one or more Y-signatures.

Abstract: The present invention relates to a method for identifying CD8+ Treg cells suitable for use as starting material in cellular immunotherapy, the method comprising i) analysing samples from target tissue A to identify CD8+ Treg cells with migratory character between the diseased tissue, collecting lymphatics, peripheral blood, distinct tissue adjacent to the diseased target tissue A and/or distinct tissue that is not vicinal though has migratory Treg communication with target tissue A, v) analysing samples from peripheral blood, tissue C, to identify CD8+ Treg cells with migratory character and/or functional character where the Treg cells are also emigrant from target tissue A, vi) analysing sample(s) from tissue compartments A and/or B and C, that are analytically or physically depleted of emigrants from thymus and/or immigrants from peripheral blood to a lymph node, to restrict analyses to CD8+ Treg cells of target tissue A origin and/or tropism, to identify emigrant CD8+ Treg cell populations of target tissue

Abstract: The present invention relates to a composition comprising an isolated CD4+ Treg cell population, wherein the Treg cells have signatures for i) identifying that the T-cells are CD4+ regulatory Tcells, ii) identifying that the Treg cells are tissue type tropic, i.e they can migrate to the diseased tissue, iii) optionally identifying that the Treg cells are tropic with respect to the diseased tissue, i.e. they are homing cells, iv) identifying that the Treg cells are emigrant cells, i.e. they originate from the target tissue, and v) optionally identifying that the Treg cells are retained in the target tissue and optionally one or more X-signatures and/or one or more Y-signatures and one ore more Z-signatures.

Abstract: The present invention relates to a method for identifying CD4+ Treg cells suitable for use as starting material in cellular immunotherapy, the method comprising i) analysing samples from target tissue A to identify CD4+ Treg cells with migratory in character between the diseased tissue, collecting lymphatics, peripheral blood, distinct tissue adjacent to the diseased target tissue A and/or distinct tissue that is not vicinal though has migratory Treg communication with target tissue A, v) analysing samples from peripheral blood, tissue C, to identify CD4+ Treg cells with migratory character and/or functional character where the Treg cells are also emigrant from target tissue A, vi) analysing sample(s) from tissue compartments A and/or B and C, that are analytically or physically depleted of emigrants from thymus and/or immigrants from peripheral blood to a lymph node, to restrict analyses to CD4+ Treg cells of target tissue A origin and/or tropism, to identify emigrant CD4+ Treg cell populations of target tis

Abstract: A method of treating inflammatory bowel disease (IBD) comprises collecting regulatory T cells in an activated or non-activated state from a patient's sentinel lymph nodes draining bowel segments with or without IBD, optionally activating the cells by contacting them with a cytokine and an antigen extract obtained from an inflamed bowel segment, expanding the T cells in vitro, and re-infusing the expanded T cell to the patient. Also disclosed are methods for obtaining sentinel nodes, for expanding T cells, for re-establishing the TH1/TH2 balance in the patient suffering from Crohn's disease, and corresponding uses of the expanded T cells, the cytokine and of antigen extract, as well as of correspondingly activated and expanded T cells.

Abstract: The present invention relates to a novel method of cancer immuno-therapy and to a kit for use in this method. Specifically, the present invention relates to a novel method of collecting lymphocytes from sentinel lumph nodes and in vitro culture for the multiplication thereof lymphocytes.

Abstract: A method of treating inflammatory bowel disease (IBD) comprises providing an intestinal biopsy sample obtained from inflamed tissue of a patient; mechanically treating the sample to obtain a cell suspension; identifying cell surface markers of activated leukocytes selected from T lymphocytes, neutrophil granulocytes, and eosinophil granulocytes in the suspension; raising antibodies against one of more of the activated cells and immobilizing them on a support; providing a column loaded with the support; diverting a portion of the patient's peripheral blood to make it pass through the column before re-infusing it to the patient to make the activated leukocytes couple with antibodies on the support, thereby eliminating them from the blood stream. Also disclosed are corresponding columns and supports, and their use in the method.

Abstract: The present invention discloses an immunotherapeutic method for treating patients suffering from malignant melanoma, by administering expanded tumour-reactive CD4+ helper and/or CD8+ T-lymphocytes obtainable from one or more sentinel or metinel lymph nodes draining a malignant melanoma or a metastasis arising from malignant melanoma. The present invention provides a new effective method for treating malignant melanoma and metastatic malignant melanoma, without adverse side effects associated with the known treatments.

Abstract: The present invention discloses an immunotherapeutic method for treating a patient suffering from a disseminated cancer by administering expanded tumour-reactive CD4+ helper and/or CD8+ T-lymphocytes obtainable from one or more metastasis-draining lymph nodes (metinel nodes) draining a metastasis. The method comprises identification of one or more metinel lymph nodes in a patient, resection of the one or more nodes and, optionally all or part of the metastases, isolation of metastasis-reactive T-lymphocytes from said lymph nodes, in vitro expansion of said metastasis-reactive T-lymphocytes, and administration of the thus obtained T-lymphocytes to the patient, wherein the T-lymphocytes are CD4+ helper and/or CD8+ T-lymphocytes.

Abstract: The present invention discloses an improved method for expansion and activation of tumor-reactive lymphocytes, in particular CD4+ helper and/or CD8+ T-lymphocytes, which may be used for treating and/or preventing cancer. The method provides high numbers of tumor-reactive T-lymphocytes within a short time span and the possibility of directing development of tumor-reactive CD4+ helper and/or CD8+ T-lymphocytes towards specific subpopulations. The method comprises a first phase of stimulating tumor-reactive CD4+ T helper and/or CD8+ T-lymphocytes with tumor-derived antigen together with at least one substance having agonistic activity towards the IL-2 receptor to promote survival of tumor-reactive CD4+ T helper and/or CD8+ T-lymphocytes; and a second phase of activating and promoting growth of tumor-reactive CD4+ T helper and/or CD8+ T-lymphocytes, wherein the second phase is initiated when the CD25 cell surface marker (or IL-2R marker) is down-regulated on CD4+ T helper and/or CD8+ T-lymphocytes.

Abstract: The present invention discloses an immunotherapeutic method for treating a patient suffering from urinary bladder cancer by administering expanded tumour-reactive CD4+ helper and/or CD8+ T-lymphocytes obtainable from one or more sentinel or metinel lymph nodes draining a tumour in the bladder or a metastasis arising from a tumour in the bladder. The method provides a new effective method for treating urinary bladder cancer and metastatic bladder cancer, without adverse side effects associated with the known treatments.

Abstract: The present invention relates to flow cytometry detection of a cancer cell or cancer cell element by binding two or more agents to extracellular markers, wherein at least one agent is cancer specific.

Abstract: Methods for treating a patient suffering from a neoplastic disease are disclosed and described. A number of diseases can be treated under the present methods, including without limitation gall bladder cancer, hepato cellular cancer, ovarian cancer, small intestine cancer, lung cancer, mesothelioma, breast cancer, kidney cancer, pancreas cancer, prostate cancer, carcinoid cancer, leiomyosarcoma, or metastasis thereof. A general method for providing such treatment may include: 1) identifying in a patient one or more sentinel and/or metinel lymph nodes draining the neoplasm; 2) resecting the one or more nodes and, optionally all or part of the tumour or metastasis; 3) isolating tumour-reactive T-lymphocytes from said lymph nodes; 4) in vitro expanding said tumour-reactive T-lymphocytes; and 5) administering the thus obtained tumour-reactive T-lymphocytes to the patient.

Abstract: Improved cancer therapy using a combination treatment with tumour-reactive T-lymphocytes obtained by an in vitro method for expansion and activation of tumour-reactive lymphocytes, in particular CD4+ helper and/or CD8+ T-lymphocytes and inhibitors of vessel formation inhibitors, notably inhibitors of VEGF.

Abstract: A method of treating inflammatory bowel disease (IBD) comprises collecting regulatory T cells in an activated or non-activated state from a patient's sentinel lymph nodes draining bowel segments with or without IBD, optionally activating the cells by contacting them with a cytokine and an antigen extract obtained from an inflamed bowel segment, expanding the T cells in vitro, and re-infusing the expanded T cell to the patient. Also disclosed are methods for obtaining sentinel nodes, for expanding T cells, for re-establishing the TH1/TH2 balance in the patient suffering from Crohn's disease, and corresponding uses of the expanded T cells, the cytokine and of antigen extract, as well as of correspondingly activated and expanded T cells.

Abstract: The present invention discloses an improved method for expansion and activation of tumour-reactive lymphocytes, in particular CD4+ helper and/or CD8+ T-lymphocytes, which may be used for treating and/or preventing cancer. The method provides high numbers of tumour-reactive T-lymphocytes within a short time span and the possibility of directing development of tumour-reactive CD4+ helper and/or CD8+ T-lymphocytes towards specific subpopulations. The method comprises a first phase of stimulating tumour-reactive CD4+ T helper and/or CD8+ T-lymphocytes with tumour-derived antigen together with at least one substance having agonistic activity towards the IL-2 receptor to promote survival of tumour-reactive CD4+ T helper and/or CD8+ T-lymphocytes; and a second phase of activating and promoting growth of tumour-reactive CD4+ T helper and/or CD8+ T-lympho-cytes, wherein the second phase is initiated when the CD25 cell surface marker (or IL-2R marker) is down-regulated on CD4+ T helper and/or CD8+ T-lymphocytes.

Abstract: The present invention discloses an immunotherapeutic method for treating patients suffering from malignant melanoma, by administering expanded tumour-reactive CD4+ helper and/or CD8+ T-lymphocytes obtainable from one or more sentinel or metinel lymph nodes draining a malignant melanoma or a metastasis arising from malignant melanoma. The present invention provides a new effective method for treating malignant melanoma and metastatic malignant melanoma, without adverse side effects associated with the known treatments.

Abstract: A method of treating inflammatory bowel disease (IBD) comprises providing an intestinal biopsy sample obtained from inflamed tissue of a patient; mechanically treating the sample to obtain a cell suspension; identifying cell surface markers of activated leukocytes selected from T lymphocytes, neutrophil granulocytes, and eosinophil granulocytes in the suspension; raising antibodies against one of more of the activated cells and immobilizing them on a support; providing a column loaded with the support; diverting a portion of the patient's peripheral blood to make it pass through the column before re-infusing it to the patient to make the activated leukocytes couple with antibodies on the support, thereby eliminating them from the blood stream. Also disclosed are corresponding columns and supports, and their use in the method.