Carbohydrate specific cellular immunity inducing microorganisms and fractions thereof
AssigneeGlycotope GmbH
InventorsSteffen Goletz, Philippe Ulsemer, Anja Löffler
Life of this patent
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Abstract
The present invention relates to the field of prevention and treatment of disorders associated with the occurrence of certain carbohydrate epitopes. The present invention relates to the prevention and treatment of carbohydrate epitope positive tumors. The invention relates to formulations and methods for the induction of an effective carbohydrate specific cellular immune response.
Claims26
Method for isolating a carbohydrate positive microorganism comprising a carbohydrate epitope of interest from a mixture of microorganisms, comprising
- (a) bringing a carbohydrate binding molecule specific for the carbohydrate epitope of interest into contact with a mixture of microorganisms, and
- (b) isolating at least one microorganism bound to said carbohydrate binding molecule from said mixture,
- (c) optionally testing that the isolated microorganism is a carbohydrate positive microorganism by testing the isolated microorganism for specific binding to said carbohydrate binding molecule.
Method according to claim 3, wherein in step (d) comprises testing the induction of an effective carbohydrate specific cellular immune response against said carbohydrate epitope by said carbohydrate positive microorganism and/or fraction and/or lysate thereof for the activation of CD4 positive Th1 type T cells and/or for the activation of cytotoxic CD8 positive T cells, preferably in at least one animal or human and/or in vitro.
The method according to any of the preceding claims wherein
- (i) the carbohydrate epitope is selected from the group comprising TF, Core-1, Tn, sialyl-Tn, sialyl-TF, Globo-H, Lewis-Y, sialyl-Lewis-A, sialyl-Lewis-X, polysialic acid, Lewis-X, GM2, GD2, GD3, 9-O-acetyl GD3, GD3L, fucosyl GM1, Fucosyl GM1, Lewis-A, Lewis-B, sLac, sialylated type 1 chain, CA 19-9 antigen, CA 72-4 antigen and CA-50 antigen, and
- (ii) the carbohydrate binding molecule is selected from the group comprising lectins, selectins, and/or antibodies and/or molecules derived therefrom which bind to TF, Core-1, Tn, sialyl-Tn, sialyl-TF, Globo-H, Lewis-Y, sialyl-Lewis-A, sialyl-Lewis-X, polysialic acid, Lewis-X, GM2, GD2, GD3, 9-O-acetyl GD3, GD3L, fucosyl GM1, Fucosyl GM1, Lewis-A, Lewis-B, sLac, sialylated type 1 chain, CA 19-9 antigen, CA 72-4 antigen or CA-50 antigen or to a carbohydrate structure comprising any of these carbohydrate epitopes or parts thereof and
A cellular immune response test comprising
- a.) Loading at least one dendritic cell with a first carbohydrate positive compound, wherein said carbohydrate positive compound carries the carbohydrate epitope of interest;
- b.) bringing into contact a suitable amount of said at least one dendritic cell loaded with said carbohydrate positive compound with a suitable amount of immune cells which can be activated or inhibited by a dendritic cell;
- c.) cultivation in order to allow interaction of said immune cells with said loaded dendritic cells;
- d.) adding a suitable amount of antigen presenting cells (APC) loaded with a suitable amount of at least one second compound carrying the same carbohydrate epitope as said first compound, wherein said second compound is different from said first carbohydrate positive compound;
- e.) cultivation for restimulation of said immune cells;
- f.) determining whether restimulation of the immune cells occurred.
A method for generation of a functional dendritic cell against a carbohydrate epitope of interest comprising bringing into contact a suitable amount of a dendritic cell or a mixture of dendritic cells or a mixture of cells comprising at least one dendritic cell with a suitable amount of a carbohydrate positive microorganism or fraction or lysate thereof of one of the claims defined herein and/or a carbohydrate structure, carbohydrate conjugate or a mammalian cell comprising said carbohydrate epitope for a suitable time under suitable conditions to generate at least one functional dendritic cell against said carbohydrate epitope and/or a carbohydrate structure, carbohydrate conjugate or a mammalian cell comprising said carbohydrate epitope.
A functional dendritic cell, an activated T cell, T cells, T cell clone or T cell line produced by the method of any of the preceding claims, wherein the activated T cell, T cells, T cell clone or T cell line is directed against the carbohydrate epitope and/or a carbohydrate structure, carbohydrate conjugate or a mammalian cell comprising said carbohydrate epitope.
A carbohydrate positive microorganism or fraction or lysate thereof comprising a carbohydrate epitope of interest which is recognized by at least one carbohydrate binding molecule specifically recognizing said carbohydrate epitope of interest, whereby said microorganism, said fraction or said lysate induces an effective carbohydrate-specific cellular immune response against said carbohydrate epitope and/or a carbohydrate structure, carbohydrate conjugate or a mammalian cell comprising said carbohydrate epitope.
A method for the immunization or vaccination of a human or an animal against a carbohydrate epitope present on a molecule from a human or animal cell comprising
- (i) administration to a human or an animal an effective amount of a functional dendritic cell, activated T cell, T cell clone or T cell line or a mixture of cells according to any of the preceding claims directed against a carbohydrate epitope of interest and induction of an immune response against the carbohydrate epitope and/or a carbohydrate structure, carbohydrate conjugate or a mammalian cell comprising said carbohydrate epitope by said cell in the human or animal (priming) and
- ii) boostering of the immune response by the administration of an effective amount of a formulation comprising at least one carbohydrate positive microorganism recognized by at least one carbohydrate binding molecule specifically recognizing a carbohydrate epitope present on a molecule from a human or animal cell, or a fraction or a lysate thereof, whereby said microorganism, said fraction or said lysate or said formulation comprising those induces an effective carbohydrate-specific cellular immune response against said carbohydrate epitope, and/or a carbohydrate structure, carbohydrate conjugate or a mammalian cell comprising said carbohydrate epitope.
A method for inducing or enhancing an effective carbohydrate specific cellular immune response and/or specific humoral immune against a carbohydrate epitope, and/or a carbohydrate structure, carbohydrate conjugate or a mammalian cell comprising said carbohydrate epitope, in at least one animal or human, comprising administering in a human or an animal an effective amount of the formulation of any of the preceding claims.
A method for prophylaxis and/or treatment of a carbohydrate epitope positive tumor and/or disease comprising administration of a suitable amount of a formulation, a carbohydrate positive microorganism, or a lysate or fraction thereof, a functional dendritic cell or an activated T cell, T cell line or T cell clone against the carbohydrate epitope and/or a carbohydrate structure, carbohydrate conjugate or a mammalian cell comprising said carbohydrate epitope according to any of the preceding claims, to a human or an animal.
Use of a carbohydrate positive microorganism isolated or identified by a method of any of the preceding claims or a fraction or a lysate thereof for manufacturing a medicament or a nutraceutical for prophylaxis and/or therapy of a disease associated with said carbohydrate epitope whereby said microorganism and/or fraction and/or lysate thereof induces an effective carbohydrate specific cellular and/or humoral immune response against said carbohydrate epitope, and/or a carbohydrate structure, carbohydrate conjugate or a mammalian cell comprising said carbohydrate epitope, in at least one animal or human.
Dependencies are inferred from the claim text.