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Last Updated: January 26, 2022

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Claims for Patent: 8,349,558

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Summary for Patent: 8,349,558
Title:Detection of individual T-cell reaction patterns against tumor-associated antigens (TAA) in tumor patients as a basis for the individual therapeutic vaccination of patients
Abstract: The present invention relates to a method for identifying the preferential target antigens of antitumoural T-cells of a tumour patient, comprising: a) providing T-cells from the blood of at least one tumour patient, b) providing dendritic cell (DCs) and/or B-lymphocytes (BLCs) that are autologous for said tumour patient, wherein said DCs and BLCs were transfected beforehand with a selection of mRNAs encoding for T-cell-immunogenic tumour-associated antigens (TAA), and express these, c) contacting said T-cells with the DCs and/or BLCs, d) identifying of those T-cells that recognize antigens of the DCs and/or BLCs, and e) identifying of the preferential target antigens of antitumoural T-cells of the at least one tumour patient on the basis of the T-cells that recognize antigens of the DCs and/or BLCs. The method can furthermore comprise the expansion of the T-cells that recognize the antigens of the DCs and/or BLCs. The present invention furthermore relates to a method for producing an individualized tumour vaccine or individualized tumour therapeutic, as well as corresponding methods for treating a tumourous disease using the individualised tumour vaccine or individualised tumour therapeutic.
Inventor(s): Fatho; Martina (Worrstadt, DE), Wesarg; Emmanuelle (Darmstadt, DE), Lennerz; Volker (Ober-Olm, DE), Van Der Bruggen; Pierre (Brussels, BE), Wolfel; Thomas (Mainz, DE), Debo; Serena (Mainz, DE)
Assignee: Johannes Gutenberg-Universitat Mainz (Mainz, DE)
Application Number:12/519,315
Patent Claims:1. A method for identifying the preferential target antigens of anti-tumoural T-cells of at least one tumour patient that is suffering from a specific tumour comprising: a) providing T cells from the blood of said at least one tumour patient, wherein the T cells are not stimulated by contact with a tumour cell line in vitro; b) providing a panel of transfected dendritic cells (DCs) and/or a panel of transfected B-lymphocytes (BLCs) for said at least one tumour patient, wherein said panel of DCs and/or BLCs are autologous DCs or autologous BLCs transfected with mRNA encoding individual T-cell tumour antigens associated with said specific tumour, wherein multiple T cell tumour antigens are represented within the panel, and wherein said mRNA is provided independent from the extraction of tumour cells from said at least one tumour patient; c) contacting the panel of transfected dendritic cells (DCs) and/or transfected B-lymphocytes (BLCs) for said at least one tumour patient with the respective autologous T cells; and d) identifying the tumour-associated antigens (TAAs) that are recognized by the T cells on the panel of transfected DCs and/or BLCs for said at least one tumour patient.

2. The method according to claim 1, further comprising the expansion of the T-cells that recognize antigens of the DCs and/or BLCs.

3. The method according to claim 1, further comprising a control assay for the reactivity of the T-cells against the TAA.

4. The method according to claim 1 further comprising determining the HLA alleles by which the recognized TAAs are presented.

5. The method according to claim 1 wherein the T cells are isolated T cells from the blood of said at least one tumour patient.

6. The method according to claim 1 wherein the mRNA encoding the tumour antigens are mRNA encoding antigens of several categories.

7. The method according to claim 6, wherein the antigens are melanocyte-specific proteins or cancer/germline-proteins (C/G-proteins).

8. The method according to claim 6 wherein the categories of tumour antigens are selected from the group consisting of differentiation antigens, cancer/germline antigens (C/G-antigens), mutated antigens and over-expressed antigens.

9. The method according to claim 8 wherein the mutated antigen is a fusion protein.

10. The method according to claim 1 wherein the specific tumour is malignant melanoma.

11. The method according to claim 6, wherein the mRNA encoding the tumour antigens includes structurally normal, "shared" TAAs.

12. The method according to claim 11, wherein said structurally normal ("shared") TAAs are selected from the group consisting of BAGE-1; GAGE-1,2,8; GAGE-3,4,5,6,7; GnTV (intron); HER V-K-MEL; KK-LC-1; KM-HN-1; LAGE-1; MAGE-A1; MAGE-A2; MAGE-A3; MAGE-A4; MAGE-A6; MAGE-A9; MAGE-A10; MAGE-A12; MAGE-C2; mucin; NA-88; NY-ESO-1/LAGE-2; SAGE; Sp17; SSX-2, SSX-4; and TRP2-INT2(intron 2).

13. The method according to claim 1 wherein the specific tumour is a tumour selected from the group consisting of kidney, breast, pancreatic, stomach, testicular, prostate, colon and skin.

Details for Patent 8,349,558

Applicant Tradename Biologic Ingredient Dosage Form BLA Approval Date Patent No. Expiredate
Merck Sharp & Dohme Corp. INTRON A interferon alfa-2b For Injection 103132 1986-06-04 ⤷  Sign up for a Free Trial 2026-12-21
Merck Sharp & Dohme Corp. INTRON A interferon alfa-2b For Injection 103132 ⤷  Sign up for a Free Trial 2026-12-21
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Approval Date >Patent No. >Expiredate

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