COMBINATION OF TUMOR-ASSOCIATED SURFACE PROTEIN ANTIGENS AND TUMOR-ASSOCIATED SUGARS IN THE TREATMENT AND DIAGNOSIS OF CANCER
The invention relates to a kit for the combined use for the treatment of cancer patients, which set comprises an antigen of a cellular surface protein, or an antibody directed against the cellular surface protein, and an antigen of an aberrant glycosylation, or an antibody directed against the aberrant glycosylation. This kit is destined both for the immunotherapeutic and the diagnostic application. The invention further relates to a selection method for selecting suitable tumor-specific antigens with the assistance of this kit and corresponding specific antibody preparations.
1 . A kit for the combined use for the treatment of cancer patients, which set comprises the following components:
a) an antigen comprising at least one epitope of a cellular surface protein, or an antibody directed against the cellular surface protein, and
b) an antigen comprising at least one epitope of an aberrant protein glycosylation, or an antibody directed against the aberrant protein glycosylation.
2 . A kit according to claim 1 , characterized in that the components a) and b) are contained in one pharmaceutical preparation each or in a single pharmaceutical preparation suitable for immunotherapy.
3 . A kit according to claim 2 , characterized in that the pharmaceutical preparation is formulated as a vaccine.
4 . A kit according to claim 2 , characterized in that the pharmaceutical preparation is formulated as an intravenously tolerable product.
5 . A kit according to claim 1 , characterized in that the antigen of component a) represents an epitope of a cellular adhesion protein, in particular of a protein selected from the group of EpCAM, NCAM and CEA.
6 . A kit according to claim 1 , characterized in that the antigen of component a) is an epitope of a surface receptor, in particular a receptor molecule selected from the group of the EGF receptor family, CD55 receptor, transferrin receptor and P-glycoprotein.
7 . A kit according to claim 1 , characterized in that the antigen of component b) represents an epitope of a carbohydrate selected from the group of Lewis antigens, in particular Lewis y and/or Lewis b, sialyl-Tn and Globe H.
8 . A kit according to claim 1 , characterized in that the antigen of component a) represents an epitope of the EpCAM molecule or of the Her-2/neu receptor, and the antigen of component b) represents an epitope of the Lewis Y molecule
9 . A method for the immunologic determination of tumor cells of a solid tumor or disseminated tumor cells of a cancer disease which comprises
a) exposing a sample from a cancer patient to:
(i) an antigen comprising at least one epitope of a cellular surface protein, or an antibody directed against the cellular surface protein, and
(ii) an antigen comprising at least one epitope of an aberrant protein glycosylation, or an antibody directed against the aberrant protein glycosylation; and
b) determining the immunological response.
10 . The method according to claim 9 , wherein the determination is carried out within the scope of the treatment of cancer patients.
11 . The method according to claim 9 , wherein said sample comprise tumor cells from samples of peripheral blood or bone marrow.
12 . The method according to claim 9 or 10 , wherein an antibody titer against the antigens of the components is determined.
13 . The method according to claim 12 , wherein the determination is carried out for monitoring a treatment of a cancer patient.
14 . A method for immunologic selection of a tumor-specific target antigen or of antibodies directed against the target antigen by exposing a sample from a cancer patient to
(a) an antigen comprising at least one epitope of a cellular surface protein, or an antibody directed against the cellular surface protein, and
(b) an antigen comprising at least one epitope of an aberrant protein glycosylation, or an antibody directed against the aberrant protein glycosylation; wherein
the antigen is a neoepitope which is formed by the glycosylaticn of an antigen of component a) with an antigen of component b).
15 . An antigen composition which comprises a neoepitope or its mimic, prepared by the method according to claim 14 .
16 . A composition according to claim 15 wherein the antigen is a naturally occurring antigen or a fragment thereof.
17 . A method according to claim 14 , wherein an antibody directed against the neoepitope is selected and prepared by using a kit according to claim 1 .
18 . An antibody composition with specificity for a neo-epitope, prepared by the method according to claim 17 .
19 . A diagnostic agent based on a kit according to claim 1 , characterized in that it contains a reagent for determining an immune reaction with components a) and b), or with antibodies against these.
20 . An agent according to claim 19 , wherein the reagent is labelled with a fluorescent agent, a chromogen, a radiolabel or an enzyme.
21 . An agent according to claim 20 , wherein the reagent is immobilized on a carrier.
22 . An agent according to claim 21 , wherein the carrier is a matrix for immunoaffinity chromatography.
23 . A kit according to claim 1 , wherein said antigen of paragraph (a) is Her2, and said antigen of paragraph (b) is Lewis Y.
24 . The method according to claim 9 , wherein the antigen of (a) is Her2, and said antigen of (b) is Lewis Y.