Use of anti cd70 antibody argx-110 to treat acute myeloid leukaemia

A myeloid leukemia and antibody technology, applied in the direction of antibody medical components, antibodies, anti-receptor/cell surface antigen/cell surface determinant immunoglobulin, etc., can solve the problem that patients are not suitable for intensive chemotherapy and the burden of chemotherapy patients, etc. problem, to achieve the effect of reducing blast cells in AML

Pending Publication Date: 2020-01-24
ARGENX BVBA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the side effects of chemotherapy can be a significant burden for patients, and many patients are not candidates for standard intensive chemotherapy

Method used

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  • Use of anti cd70 antibody argx-110 to treat acute myeloid leukaemia
  • Use of anti cd70 antibody argx-110 to treat acute myeloid leukaemia
  • Use of anti cd70 antibody argx-110 to treat acute myeloid leukaemia

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Experimental program
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specific Embodiment approach

[0090]As demonstrated herein, patients with myeloid neoplasms, such as AML and MDS, can be treated with anti-CD70 antibodies. After a single administration of the anti-CD70 antibody, the number of leukemia stem cells capable of being isolated from the subject's bone marrow was significantly reduced, as was the number of blasts detected in the bone marrow and peripheral blood. This result was observed even at surprisingly low antibody doses.

[0091] Accordingly, in a first aspect, the present invention provides a method for treating acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) in a subject, said method comprising administering to said subject One or more doses of the anti-CD70 antibody or antigen-binding fragment thereof are administered. The present invention provides a method for treating acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) in a subject, said method comprising administering to said subject one or more therapeutically effe...

Embodiment 1

[0207] Example 1: Anti-CD70 Antibody Monotherapy or Combination with Decitabine on Human AML Transplanted in Mice The role of LSC

[0208] Transplant 5 × 10 into NSG mice 6 CD45 暗 SSC lo Human AML cells. At 32 days post-implantation (implantation in PB: 14.45% + / - 0.95%), NSG mice were randomized to receive vehicle (Veh), aCD70 mAb (aCD70, ARGX-110, 10 mg / kg), ground Citabine (D, 1.5 mg / kg / day) or combination (aCD70 / D) treatment was continued for 5 days and bone marrow, spleen and blood were analyzed.

[0209] Both anti-CD70 and decitabine alone caused decreased total engraftment in bone marrow, spleen and blood ( figure 1 ). The combination of anti-CD70 and decitabine enhanced the reduction in the percentage of engrafted human cells compared to either therapy alone ( figure 1 ).

[0210] The combination therapy also reduced CD34+ AML cells (a marker of progenitor cells) in the bone marrow better than decitabine or anti-CD70 alone ( figure 1 ). Furthermore, anti-C...

Embodiment 2

[0211] Example 2: Hypomethylating agent (HMA) upregulates CD70 expression on primary AML stem cells in vitro and in vivo, which is consistent with The combination of anti-CD70 antibody and HMA enhances the reduction of AML colony formation

[0212] Further studies in primary human AML LSCs found that anti-CD70 antibody treatment in combination with nucleoside metabolism inhibitors (NMIs), such as the hypomethylating agent decitabine, enhanced AML blast engraftment in mice reduction.

[0213] The effect of NMI treatment (for example HMA such as azacitidine or decitabine) on CD70 expression of AML LSCs was investigated. CD34+CD38- cells were isolated from AML patients and cultured in the presence of 0.5 mM decitabine or vehicle.

[0214] figure 2 Data in A demonstrates increased CD70 expression of AML LSC cells when cells were cultured with decitabine. This increase in CD70 expression in response to decitabine occurred in cells obtained from AML patients in all disease r...

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Abstract

The present disclosure relates to methods of treating acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) using an anti CD70 (ARGX-110) alone or in combination with a hypomethylating agent.

Description

technical field [0001] The present invention relates to methods of treating acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS) and compositions and combinations suitable for use in said methods. Background technique [0002] Acute myelogenous leukemia (AML) is a heterogeneous disease characterized by uncontrolled clonal expansion of hematopoietic progenitor cells. AML is the most common acute leukemia affecting adults, with an annual incidence in European adults of 5 to 8 cases per 100,000 individuals and a sharp increase in the age group over 70 years, where the incidence reaches 15 Cases - 25 cases / 100,000 people. [0003] Survival statistics published by Cancer Research UK for AML of all ages diagnosed in the UK between 2008 and 2010 show that around 20% of subjects survive 5 years or more after diagnosis longer. Prognostic factors for adverse outcome included subject's age, history of treatment-induced AML and myelodysplastic syndrome, or another pri...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/28A61K39/00
CPCA61K31/706A61K35/28A61K39/001138A61K39/39558A61K45/06A61K2039/505A61K2039/545A61P35/00A61P35/02C07K16/2875C07K2317/21C07K2317/22C07K2317/24C07K2317/41C07K2317/732C07K2317/734C07K2317/76C07K2317/90C07K2317/94A61K2300/00
Inventor N·勒平L·范罗姆帕伊H·德哈德A·奥赫森拜因C·里特
Owner ARGENX BVBA
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