A combination of compositions for elimination and enhanced engraftment of hematopoietic stem cells in the bone marrow of a subject

A technology of hematopoietic stem cells and compositions, which can be used in drug combinations, extracellular fluid diseases, medical raw materials derived from mammals, etc., and can solve problems such as intolerance

Pending Publication Date: 2021-09-03
ミルテニイビオテックベーファーウントコーカーゲー
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Administration of chemotherapy is acceptable in this setting when the underlying disease is malignant, but highly inadvisable in the setting of non-malignant monogenic disorders such as aplastic anemia, primary immunodeficiency, and hemoglobinopathies
Furthermore, such conditioning is completely intolerable in DNA repair deficient patients predisposed to hematopoietic malignancies such as ataxia telangiectasia, Bloom syndrome, and Fanconi anemia

Method used

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  • A combination of compositions for elimination and enhanced engraftment of hematopoietic stem cells in the bone marrow of a subject
  • A combination of compositions for elimination and enhanced engraftment of hematopoietic stem cells in the bone marrow of a subject
  • A combination of compositions for elimination and enhanced engraftment of hematopoietic stem cells in the bone marrow of a subject

Examples

Experimental program
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Embodiment

[0177] Example #1: Binding to CD20 Positive Jeko 1 The antigen recognition portion Z of the CD20 antigen on the cell (CD20 Function of Fab) conjugated and stained with fluorescent anti-biotin APC biotin-crosslinker YCD20 positive Jeko-1 cells were seeded in 96-well plates (50.000 cells / well) and conjugated with biotin-crosslinker at different concentrations (0,01-100 μg / ml and 0 μg / ml as negative control) Anti-CD20 Fab (Rtx Fab MS2) was incubated in a total volume of 50 μl buffer A (CliniMACS PBS / EDTA buffer + 0.5% BSA) for 10 min at 4°C. After the addition of 50 μl Antibiotin APC (1:50 in Buffer A, Miltenyi Biotec, Art. No. 130-110-952), the samples were incubated for a further 10 min at 4°C. Anti-human CD20 APC conjugate as a positive control was used to stain control samples according to the manufacturer's protocol (Miltenyi Biotec, Art. No. 130-111-525). Finally, 100 μl of buffer A was added to each sample and data was collected on MACSQuant Analyzer 10 (Miltenyi Bio...

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Abstract

The present invention provides a combination of compositions comprising i) a composition comprising I) a population of T cells, NK cells or cytotoxic immune effector cells comprising a chimeric antigen receptor specific for a stem cell antigen and / or, II) alpha) a population of T cells, NK cells or cytotoxic immune effector cells comprising a chimeric antigen receptor specific for a tag of a tagged polypeptide, wherein said tagged polypeptide binds specifically to a stem cell antigen, and beta) said tagged polypeptide, and ii) a composition comprising a) a population of CD34+ hematopoietic stem cells, and b) one or more accessory or contributory cell populations selected from the group consisting of myeloid cell lineages expressing CD14, CD11b, CD11c, CD123, CD33; CD36; CD47, CD66b, CD235a, CD146 and CD326. A method applying these compositions to a subject in need thereof are also provided.

Description

Background technique [0001] Hematopoietic stem cell (HSC) transplantation has been used to treat hematological malignancies for more than 50 years. Recipients of allogeneic hematopoietic stem cell transplantation must undergo so-called "conditioning" prior to transplantation to weaken their own hematopoietic function so that the donor hematopoietic cells can engraft, that is, migrate to the recipient's bone marrow (BM) and proliferate. Conditioning regimens for allogeneic transplantation typically include myeloablative and lymphodepletive regimens aimed at reducing the disease burden by eradicating malignant cells while immunosuppressing the recipient's lymphoid cells to allow robust and sustained donor hematopoietic stem cell engraftment. enter. The standard clinical treatment is alkylating agents and lymphodepleting agents, and the process usually includes high-dose chemotherapy combined with whole-body irradiation to induce very high stem cell and immune cytotoxicity. Suc...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/00A61P37/02A61P35/00A61P7/06A61P7/00
CPCA61K35/17A61K35/28A61P35/00A61K2300/00
Inventor E·帕帕尼科拉乌S·米尔泰伊A·博西奥M·阿森马赫尔A·凯泽
Owner ミルテニイビオテックベーファーウントコーカーゲー
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