Method for ex-vivo purging in autologous transplantation

A technology of autologous transplantation and ligands, applied in biochemical equipment and methods, biological agents for removing bad cells, cells modified by introducing foreign genetic material, etc.

Inactive Publication Date: 2007-09-05
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0013] To date, none of the above-mentioned approaches has been demonstrated to meet the requirements for complete elimination of residual tumor cells while maintaining hematopoietic and lymphoid function of the autograft

Method used

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  • Method for ex-vivo purging in autologous transplantation
  • Method for ex-vivo purging in autologous transplantation
  • Method for ex-vivo purging in autologous transplantation

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Experimental program
Comparison scheme
Effect test

Embodiment Construction

[0108] MegaFasL induces high levels of apoptosis in hematological malignancies

[0109] IC determined from PESMTS assay 50 shown in Figure 3. Values ​​represent means (±SEM) of 3 independent experiments. ND = no data available; resistance = IC 50 Fas agonist concentrations up to 10,000 ng / ml were not achieved.

[0110] disease

cell name

MegaFasL

IC 50 (ng / ml)

CH11

IC 50 (ng / ml)

sFasL M2

IC 50 (ng / ml)

multiple myeloma

ARH-77

RPMI-8226

U266

OPM2

10.4±0.19

3.57±0.68

6.20±1.50

2.19±1.53

resistance

resistance

resistance

ND

136±12.0

ND

39.9±10.1

ND

acute myeloid leukemia

HL60(AML-M3)

NB4 (AML-M3)

213±126

16.0±3.18

resistance

resistance

ND

resistance

acute T lymphoblastic leukemia

Jurkat

0.06±0.03

6.58±2.57

6.36±1.93

Burkitt Lymphoma

...

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Abstract

The present invention concerns a new method for ex-vivo purging of cells in autologous transplantation, wherein the sample of taken cells is treated with a sufficient amount of a multimeric form of the soluble portion of FasL to kill malignant cells without substantially affecting viability of cells to be transplanted. Autologous stem cell transplantation (ASCT) following high-dose chemotherapy with or without radiotherapy has become the standard therapy for the majority of patients with large-cell lymphomas, multiple myeloma, and refractory / recidivating Hodgkin's disease. Such therapy is nowadays also contemplated for selected patients with low-grade lymphomas (chronic lymphocytic leukemia, follicular lymphoma, mantle cell lymphoma) and for patients with acute myeloid leukemia (AML). Current treatments for cell purging include chemotherapy and antibody cocktails. These treatments are often toxic on stem cells and not efficient in eliminating cancer cells. Thus, there is an unmet medical need for cell purging in ASCT which this project will address.

Description

technical field [0001] The present invention relates to a novel method for ex vivo purification of cells in autologous transplantation, wherein a sample of harvested cells is treated with a soluble fraction of FasL in multimeric form in sufficient quantities to kill malignant cells without substantially affecting Viability of cells to be transplanted. Background technique [0002] Autologous stem cell transplantation (ASCT) combined with high-dose chemotherapy with (or without) radiation therapy has become the treatment of choice for most patients with large cell lymphoma, multiple myeloma, and refractory / relapsed Hodgkin's disease. standard therapy for patients. It is now also intended to apply this therapy to selected patients with low-grade lymphomas (chronic lymphocytic leukemia, follicular lymphoma, mantle cell lymphoma) and patients with acute myeloid leukemia (AML). Current treatments for cell purification include chemotherapy and antibody cocktails. These treatmen...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N5/16
CPCC12N5/0093C12N5/00C12N5/0693C12N5/0647
Inventor 马克·迪皮伊彼得·格雷亚内迈克尔·迪肖扎尔
Owner APOXIS
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