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Combination of anti cd19 antibody with a bcl-2 inhibitor and uses thereof

An antibody and sequence technology, applied in the direction of antibodies, drug combinations, antibody medical components, etc., can solve problems such as poor prognosis of cancer

Pending Publication Date: 2019-06-14
MORFOZIS AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0015] Despite recent advances in the discovery and development of anticancer drugs, many forms of cancer involving CD19-expressing tumors still have a poor prognosis

Method used

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  • Combination of anti cd19 antibody with a bcl-2 inhibitor and uses thereof
  • Combination of anti cd19 antibody with a bcl-2 inhibitor and uses thereof
  • Combination of anti cd19 antibody with a bcl-2 inhibitor and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach

[0070] One aspect of the disclosure is a combination comprising a CD19-specific antibody and BCL-2 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 venetoclax acts synergistically in an in vitro model of CLL. Since CLL is a B cell related disease and CD19 is highly expressed on B cells, the exemplified combinations should have the same mechanism of action and should also work synergistically in the treatment of other B cell related diseases such as ALL and NHL. Therefore, the combination of the exemplified CD19-specific antibodies and venetoclax will be effective in the treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia and / or acute lymphoblastic leukemia in humans. The expected efficacy of the exemplified combination of CD19-specific antibody and venetoclax will be confirm...

Embodiment 1

[0100] Example 1 : Cytotoxicity of MOR00208 and venetoclax alone and in combination in MEC-1 cells

[0101] Material

[0102] Cell line tested: MEC-1 cells (DSMZ #ACC497). Use the culture conditions of the cell lines according to the supplier's information. Cell culture medium: Iscove's modified Dulbecco medium (IMDM), Invitrogen, Cat No.:31980; RPMI1640, Invitrogen, Cat No.:31870; GlutaMAX, Invitrogen, CAT No.:35050; FCS: SigmaCAT No.:F7524LOT No .:111M3396. NKs: RPMI1640 with GlutaMAX, Invitrogen, Cat No.:31870, 10% FCS; Biocoll: Biochrome AG CAT No.:L6115LOT No.:0034D; MACS NK Cell Isolation Kit: Miltenyi Biotec CAT No.:130-092- 657LOT No.:5150402327; Venetoclax: SelleckChem.CAT No.:S8048LOT No.:S804803; FCS: Sigma CAT No.:F7524 LOT No.:111M3396; and RefmAb33 (anti-RSV), the same Fc region as MOR00208 .

[0103] method

[0104] The cytotoxic potential of MOR00208 and venetoclax alone and in combination was tested in the MEC-1 cell line (CLL). Target cell killin...

Embodiment 2

[0151] Example 2: MOR00208 combined with ABT-199 in SCID mice in subcutaneous human lymphoma cell xenograft model potency in type

[0152] The efficacy benefit of MOR00208 in combination with venetoclax (ABT-199) was further investigated in a SCID mouse model with subcutaneous TOLEDO human lymphoma cell tumors. Tumor growth and mortality were assessed.

[0153] Materials & Methods

[0154] The Toledo cell line and media were purchased from Oncodesign. tumor cells in a humidified atmosphere (5% CO 2 , 95% air) at 37°C to grow as monolayers. The medium is supplemented with 10% fetal bovine serum (ref: P30-1506, Lonza), HBSS (ref: BE10-543F), glucose (ref: G8769, Sigma, France), Hepes (ref: BE17-737E, Lonza) RPMI 1640 containing 2 mM L-glutamine (ref: BE12-702F, Lonza, Verviers, Belgium) and sodium pyruvate (ref: BE13-115E, Lonza). Cells are attached to plastic bottles. For experimental purposes, tumor cells were removed from culture flasks by treating with trypsin-ve...

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Abstract

The present disclosure describes a pharmaceutical combination of an anti-CD19 antibody and a BCL-2 inhibitor for the treatment of non-Hodgkin lymphoma, chronic lymphocytic leukemia and / or acute lymphoblastic leukemia.

Description

field of invention [0001] The present disclosure relates to pharmaceutical combinations of anti-CD19 antibodies and BCL-2 inhibitors for the treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia and / or acute lymphoblastic leukemia. Background technique [0002] 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 produce antibodies against various antigens and is an essential component of the adaptive immune system. [0003] 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 disorders include non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL). [0004] NHL is a heterogeneous malignancy derived from lymphocytes. In the United Sta...

Claims

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Application Information

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IPC IPC(8): A61K39/395A61K31/00C07K16/28A61P35/00
CPCA61K39/395A61K31/496C07K16/2803A61P35/02A61K2300/00A61K39/3955A61K31/635A61K2039/505A61K9/0019
Inventor J·恩德尔K·帕特普洛斯P·凯莱门R·博克斯哈默M·吕克特
Owner MORFOZIS AG
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