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Combination therapy with anti-CD19 antibody and purine analog

An antibody and sequence technology, applied in the field of combination therapy using anti-CD-19 antibody and purine analogues, can solve problems such as poor prognosis of cancer

Active Publication Date: 2014-04-02
MORFOZIS AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0019] Clearly, despite recent advances in the discovery and development of anticancer agents, many forms of cancer involving CD19-expressing tumors still have a poor prognosis

Method used

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  • Combination therapy with anti-CD19 antibody and purine analog
  • Combination therapy with anti-CD19 antibody and purine analog
  • Combination therapy with anti-CD19 antibody and purine analog

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach

[0070] One aspect of the disclosure includes a combination of a CD19-specific antibody and a purine analog for use in the treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia, and / or acute lymphoblastic leukemia. In an embodiment, the combination is synergistic.

[0071] Here, the exemplified combination of an anti-CD19 antibody and fludarabine acts synergistically in in vitro and in vivo models associated with NHL and CLL. Since both NHL and CLL are B cell related disorders and CD19 is highly expressed on B cells, the exemplified combination should have the same mechanism of action in the treatment of other B cell related disorders such as ALL and should also work synergistically effect. Thus, the exemplified CD19-specific antibody in combination with fludarabine will be effective in the treatment of human non-Hodgkin's lymphoma, chronic lymphocytic leukemia and / or acute lymphoblastic leukemia.

[0072] Since the mechanisms of action of fludarabine and other pu...

Embodiment 1

[0087] Example 1 : MOR208 and fludarabine alone and in combination inhibit the proliferation of MEC-1 cells

[0088] Material

[0089] MEC-1 cells: chronic B-cell leukemia cell line DSMZ#ACC497; cell culture medium: with GlutaMAX TM Iscove's Modified Dulbecco's Medium (IMDM), Invitrogen, Cat No.: 31980-048, 20% FCS; PBMC: RPMI1640 with stabilized glutamine, PAN Biotech GmbH, Cat No.: P04-13500 supplemented with 10 %FCS; Biocoll: Biochrome AG CAT No.:L6115LOT No.:1050T; Fludarabine: Bayer, 25mg / ml in ddH2O, LOT No.:9100ST; and RefmAb33 (anti-RSV), Fc region same as MOR208 .

[0090] method

[0091] The cytotoxicity of MOR208 and fludarabine alone and in combination was tested in MEC-1 cells. FLU is a purine analog and thus acts via direct cytotoxicity in MEC-1 cells. MOR208 targets CD19 and additionally functions via ADCC in the killing of MEC-1 cells. MEC-1 cell killing was measured in the following groups: FLU, 18 μg / ml; MOR208, 66pm; and the combination of MOR208...

Embodiment 2

[0123] Example 2 : MOR208 and FLU alone and in combination were subcutaneously (SC)-implanted into a human Ramos Burkitt's B-cell lymphoma tumor growth model.

[0124] Material

[0125] RAMOS human Burkitt's lymphoma cells (ATCC number CRL-1596, lot #3953138); vehicle control: 0.9% NaCl, 25mg / mL mannitol, pH7.0; SCID mice (University of Adelaide, Waite Campus, Urrbaraie, SA, Australia, strain C.B.-17-Igh-1 b -Prkdc scid ).

[0126] method

[0127] Subcutaneously implant RAMOS cells (~5x10 6 cells / mouse). Fourteen days after inoculation, the mice were divided into 10 groups of 8 each, wherein each group had tumor volumes of relatively the same size. Treatment started on day 14. Treatment regimens are provided in Table 4. The study duration was 63 days.

[0128] Table 4

[0129]

[0130] MOR208, fludarabine and vehicle were all administered in a volume of 0.1 mL / 10 g body weight. The initial readout was tumor growth, specifically tumor volume on study day 3...

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Abstract

The disclosure describes a pharmaceutical combination of an anti-CD19 antibody and a purine analog for the treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia and / or acute lymphoblastic leukemia.

Description

[0001] cross reference [0002] This application claims the benefit of US Provisional Patent Application No. US 61 / 523,862, filed August 16, 2011, which is hereby incorporated by reference in its entirety. field of invention [0003] The present disclosure relates to pharmaceutical combinations of an anti-CD19 antibody and a purine analogue for the treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia and / or acute lymphoblastic leukemia. Background technique [0004] B cells are lymphocytes that play a major role in the humoral immune response. They are produced in the bone marrow of most mammals and represent 5-15% of the circulating lymphoid pool. The main function of B cells is to make antibodies against different antigens and is an essential part of the adaptive immune system. [0005] Due to their critical role in regulating the immune system, disregulation of B cells is associated with a variety of disorders, such as lymphomas and leukemias. These disor...

Claims

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Application Information

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IPC IPC(8): C07K16/28A61K39/395
CPCC07K16/2803A61K2039/505A61P35/00A61P35/02A61K31/7076A61K39/3955A61K2300/00A61K39/395
Inventor J·阿默斯道费尔S·施泰德尔M·温德尔里奇S·科龙L·罗伊杰尔
Owner MORFOZIS AG
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