Combination of the application of antibodies for immunostimulation together with glucocorticoids

• US 8,709,421 B2
• Filed: 10/26/2007
• Issued: 04/29/2014
• Est. Priority Date: 04/26/2005
• Status: Active Grant

• Current Assignee: Lindis Biotech GmbH
• Original Assignee: Trion Pharma GmbH
• Inventors: Heiss, Markus M., Lindhofer, Horst
• Primary Examiner(s): Sang, Hong
• Application Number:
  US11/977,856
• Publication Number:
  US 20090191201A1
• Time in Patent Office: 2,377 Days
• Field of Search: None
• US Class Current: 424/136.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/001106 Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ErbB4
• CPC Class Codes: A61K 39/001112 CD19 or B4
• CPC Class Codes: A61K 39/001113 CD22, BL-CAM, siglec-2 or sialic acid- binding Ig-related lectin 2
• CPC Class Codes: A61K 39/001124 CD20
• CPC Class Codes: A61K 39/001128 CD44 not IgG
• CPC Class Codes: A61K 39/001129 Molecules with a "CD" designation not provided for elsewhere
• CPC Class Codes: A61K 39/001135 Vascular endothelial growth factor [VEGF]
• CPC Class Codes: A61K 39/001166 Adhesion molecules, e.g. NRCAM, EpCAM or cadherins
• CPC Class Codes: A61K 39/001171 Gangliosides, e.g. GM2, GD2 or GD3
• CPC Class Codes: A61K 39/001182 Carcinoembryonic antigen [CEA]
• CPC Class Codes: A61K 39/001186 MAGE
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 16/2809 against the T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 16/32 : against translation products of oncogenes
• CPC Class Codes: C07K 2317/31 : multispecific

Abstract

The present invention relates to methods for reducing or eliminating the non-specific release of a cytokine associated with a disease comprising administering at least one glucocorticoid and an immunostimulating antibody. Additionally, the present invention relates to a pharmaceutical composition that contains at least one immunostimulating antibody and at least one glucocorticoid.

Claims

1. A method for reducing the non-specific release of a cytokine in a subject which is associated with a treatment of a cancer or tumor with an antibody comprising administering to the subject at least one glucocorticoid immediately before or immediately after administering at least one trifunctional, bispecific immunostimulating antibody directed against a tumor antigen and a CD marker, which glucocorticoid reduces the non-specific release of the cytokine associated with the treatment of the cancer or tumor, wherein the CD marker is selected from the group consisting of CD2, CD3, CD4, CD5, CD6, CD8, CD28, and CD44.

2. The method of claim 1 which alleviates the side effects associated with treatment of the cancer or tumor with the at least one immunostimulating trifunctional, bispecific antibody (trAB).

3. The method of claim 1, wherein the glucocorticoid is selected from the group consisting of prednisone, prednisolone, methylprednisolone, triamcinolone, betamethasone, dexamethasone, cortisone acetate, prednylidene, deflazacort, cloprednol, fluocortolone and budenoside.

4. The method of claim 1, wherein a combination of glucocorticoids is administered and is selected from the group consisting of prednisone, prednisolone, methylprednisolone, triamcinolone, betamethasone, dexamethasone, cortisone acetate, prednylidene, deflazacort, cloprednol, fluocortolone and budenoside.

5. The method of claim 1, wherein the cancer is selected from the group consisting of gastric carcinoma, adenocarcinoma, malignant melanoma, colonic carcinoma, pancreatic carcinoma, ovarian carcinoma, uterine carcinoma, hepatocellular carcinoma, all histological types of bronchial carcinoma, lymphomas, sarcomas, blastomas and gastrointestinal stromal tumour (GIST).

6. The method of claim 1, wherein the antibody is a monoclonal antibody, a chimeric antibody or a humanised antibody.

7. The method of claim 1 which permits increased antibody administration during a cancer treatment.

8. The method of claim 1, wherein the tumour antigen is selected from the group consisting of EpCAM, HER2/neu, HER3/neu, G250, CEA, MAGE, VEGF, GD3, EGFR, α

Vβ

3-integrin, HLA, HLA-DR, ASC, CD1, CD7, CD11, CD13, CD14, CD19, CD20, CD21, CD22, CD23, CD24, CD33, CD40, CD41, CD52, c-erb-2, CALLA, MHCII, CD44v3, CD44v6, CD117, p97, ganglioside GD2, GD3, C215, antigen of the antibody 9.2.27, antigen of the antibody NE150 and antigen of the antibody CA125.

9. The method of claim 6, wherein the antibody has the specificity of anti-EpCAM×

anti-CD3 or anti-HER2/neu×

anti-CD3.

10. The method of claim 1, wherein the antibody and/or the glucocorticoid is/are administered intraperitoneally, intravenously, intra-arterially, intramuscularly, intradermally, subcutaneously, intratumourally or selectively into a defined organ.

11. The method of claim 10, wherein the selective administration into a defined organ is undertaken via a catheter into the supplying vessel.

12. The method of claim 11, wherein the defined organ is a liver and administration into the liver is undertaken via a catheter into the A. hepatica.

13. A method for reducing the non-specific release of a cytokine in a subject which is associated with a treatment of a cancer or tumor with an antibody comprising administering to the subject at least one glucocorticoid concurrently with at least one trifunctional, bispecific immunostimulating antibody directed against a tumor antigen and a CD marker, which glucocorticoid reduces the non-specific release of the cytokine associated with the treatment of the cancer or tumor, wherein the CD marker is selected from the group consisting of CD2, CD3, CD4, CD5, CD6, CD8, CD28, and CD44.

14. The method of claim 13, wherein the glucocorticoid and the immunostimulating antibody are separated from each other.

15. A method of permitting increased antibody administration during a cancer treatment of a subject comprising administering to the subject at least one glucocorticoid immediately before, concurrently or immediately after treatment with at least one trifunctional, bispecific immunostimulating antibody directed against a tumor antigen and a CD marker which glucocorticoid reduces the non-specific release of cytokines associated with the antibody treatment, wherein the CD marker is selected from the group consisting of CD2, CD3, CD4, CD5, CD6, CD8, CD28, and CD44.