Compositions and methods for treatment of hematological malignancies

• US 9,388,230 B2
• Filed: 09/28/2011
• Issued: 07/12/2016
• Est. Priority Date: 09/28/2010
• Status: Active Grant

• Current Assignee: KAHR Medical (2005) Ltd.
• Original Assignee: Hadasit Medical Research Services and Development Limited, KAHR Medical (2005) Ltd.
• Inventors: Dranitzki Elhalel, Michal
• Primary Examiner(s): Carlson, Karen Cochrane
• Application Number:
  US13/824,423
• Publication Number:
  US 20140147462A1
• Time in Patent Office: 1,749 Days
• Field of Search: 530/350
• US Class Current: 1/1
• CPC Class Codes: A61K 38/1774 Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: C07K 14/70521 CD28, CD152
• CPC Class Codes: C07K 14/70575 NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154 NGF C07K14/48, TNF C07K14/525
• CPC Class Codes: C07K 14/70578 NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 NGF-receptor C07K14/71, TNF-receptor C07K14/7151
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/21 containing a His-tag
• CPC Class Codes: C07K 2319/33 fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies

Abstract

Use of a chimeric protein selected from the group consisting of CTLA4-FasL and CD40-FasL proteins for treatment of lymphoma and/or a multiple myeloma and/or a leukemia as described herein, and pharmaceutical compositions and methods of treatment thereof.

Claims

1. A method of treatment of lymphoma in a subject, comprising administering to the subject a CTLA4-FasL chimeric protein.

2. The method of claim 1, wherein said lymphoma is selected from the group consisting of a malignant growth of B or T cells in the lymphatic system, Hodgkin'"'"'s lymphoma non-Hodgkin'"'"'s lymphoma (NHL).

3. The method of claim 2, wherein the non-Hodgkin'"'"'s Lymphoma is selected from the group consisting of aggressive NHL, transformed NHL, indolent NHL, pre-malignant NHL, relapsed NHL, refractory NHL, low grade non-Hodgkin'"'"'s Lymphoma, follicular lymphoma, large cell lymphoma, B-cell lymphoma, T-cell lymphoma, Mantle cell lymphoma, Burkitt'"'"'s lymphoma, NK cell lymphoma, diffuse large B-cell lymphoma, acute lymphoblastic lymphoma, cutaneous T cell cancer, and mycosos fungoides/Sezry syndrome.

4. The method of claim 3, wherein said indolent non-Hodgkin'"'"'s Lymphoma (NHL) is selected from the group consisting of a slow growing form of lymphoma, a low grade NHL and an intermediate grade NHL.

5. The method of claim 4, to halt the progression of the disorder to a malignant form of multiple myeloma.

6. The method of claim 1, wherein said administering said chimeric protein to the subject comprises administering said chimeric protein to the subject already afflicted with said lymphoma, prone to said lymphoma or as maintenance therapy, or to halt progression of the lymphoma.

7. The method of claim 1, wherein said chimeric protein is administered as a pharmaceutical composition comprising said chimeric protein and a pharmaceutical carrier, adapted for treatment of lymphoma.

8. The method of claim 7, wherein said lymphoma is selected from the group consisting of a malignant growth of B or T cells in the lymphatic system, Hodgkin'"'"'s lymphoma and non-Hodgkin'"'"'s lymphoma (NHL).

9. The method of claim 8, wherein the non-Hodgkin'"'"'s Lymphoma is selected from the group consisting of aggressive NHL, transformed NHL, indolent NHL, pre-malignant NHL, relapsed NHL, refractory NHL, low grade non-Hodgkin'"'"'s Lymphoma, follicular lymphoma, large cell lymphoma, B-cell lymphoma, T-cell lymphoma, Mantle cell lymphoma, Burkitt'"'"'s lymphoma, NK cell lymphoma, diffuse large B-cell lymphoma, acute lymphoblastic lymphoma, cutaneous T cell cancer, and mycosos fungoides/Sezry syndrome.

10. The method of claim 9, wherein said indolent non-Hodgkin'"'"'s Lymphoma (NHL) is selected from the group consisting of a slow growing form of lymphoma, a low grade NHL and an intermediate grade NHL.

11. The method of claim 9, to halt the progression of the disorder to a malignant form of multiple myeloma.

12. The method of claim 1, wherein the effect of said chimeric protein comprises an anti-proliferative effect or apoptotic effect, or a combination thereof.

13. The method of claim 12, wherein said effect further comprises sensitizing cancer cells to said effect of chimeric protein by said chimeric protein.