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Strategies for purging CD96(+) stem cells in vitro and in vivo: New avenues for autologous stem cell transplantation in acute myeloid leukemia.

Staudinger M, Humpe A, Gramatzki M - Oncoimmunology (2013)

Bottom Line: The persistence of leukemic stem cells (LSCs) in acute myeloid leukemia (AML) patients receiving chemotherapy may be responsible for the high frequency of relapse.The selective elimination of CD96(+) AML-LSCs by means of CD96-specific monoclonal antibodies may be a promising therapeutic approach and revitalize autologous hematopoietic progenitor cell transplantation.

View Article: PubMed Central - PubMed

Affiliation: Division of Stem Cell Transplantation and Immunotherapy; 2nd Department of Medicine; Christian-Albrechts-University of Kiel; Kiel, Germany.

ABSTRACT
The persistence of leukemic stem cells (LSCs) in acute myeloid leukemia (AML) patients receiving chemotherapy may be responsible for the high frequency of relapse. The selective elimination of CD96(+) AML-LSCs by means of CD96-specific monoclonal antibodies may be a promising therapeutic approach and revitalize autologous hematopoietic progenitor cell transplantation.

No MeSH data available.


Related in: MedlinePlus

Figure 1. Strategies to purge acute myeloid leukemia stem cells in autologous stem cell grafts and patients. (A) The depletion of acute myeloid leukemia (AML) leukemic stem cells (LSCs, red) from autologous hematopoietic progenitor cells (HPCs, blue) grafts in vitro may be achieved by means of a MicroBead-coupled antibody targeting an AML stem cell antigen and the magnetic-activated cell sorting (MACS) technology. (B) Chimeric antibodies carrying a human Fc portion and binding to an AML-specific antigen may recruit autologous or allogeneic natural killer (NK) cells in patients and trigger the elimination of AML-LSCs via antibody-dependent cellular cytotoxicity (ADCC).
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Figure 1: Figure 1. Strategies to purge acute myeloid leukemia stem cells in autologous stem cell grafts and patients. (A) The depletion of acute myeloid leukemia (AML) leukemic stem cells (LSCs, red) from autologous hematopoietic progenitor cells (HPCs, blue) grafts in vitro may be achieved by means of a MicroBead-coupled antibody targeting an AML stem cell antigen and the magnetic-activated cell sorting (MACS) technology. (B) Chimeric antibodies carrying a human Fc portion and binding to an AML-specific antigen may recruit autologous or allogeneic natural killer (NK) cells in patients and trigger the elimination of AML-LSCs via antibody-dependent cellular cytotoxicity (ADCC).

Mentions: In this context, the discrimination of normal HSCs and residual AML-LSCs is a stringent prerequisite. While both AML-LSCs and HSCs are characterized by the surface expression of CD34 and the lack of CD38,1 other antigens including CD33, CD44, CD123, CD47 and CLL-1 seem to be preferentially expressed by AML-LSCs.6 The potential use of monoclonal antibodies specific for these markers is limited by their expression on other cell types, which may result in very severe side effects. CD96 (TACTILE) has originally been detected on AML-LSCs, and its expression was confirmed on the majority of AML blasts in 30% of patients.7,8 Importantly, the expression of CD96 on healthy HSCs is low or absent. In addition, CD96 is expressed by activated T and NK cells, where it may be involved in the adhesion between effector and tumor cells.9 Although the physiological functions of CD96 on AML-LSCs are actually unknown, it may contribute to their adhesion to the bone marrow compartment. On the basis of the CD96 expression pattern and properties, we selected CD96 for the development of antibody-based strategies for the depletion of AML-LSCs from autologous HPC grafts ex vivo and for the elimination of CD96+ cells in patients (Fig. 1).10


Strategies for purging CD96(+) stem cells in vitro and in vivo: New avenues for autologous stem cell transplantation in acute myeloid leukemia.

Staudinger M, Humpe A, Gramatzki M - Oncoimmunology (2013)

Figure 1. Strategies to purge acute myeloid leukemia stem cells in autologous stem cell grafts and patients. (A) The depletion of acute myeloid leukemia (AML) leukemic stem cells (LSCs, red) from autologous hematopoietic progenitor cells (HPCs, blue) grafts in vitro may be achieved by means of a MicroBead-coupled antibody targeting an AML stem cell antigen and the magnetic-activated cell sorting (MACS) technology. (B) Chimeric antibodies carrying a human Fc portion and binding to an AML-specific antigen may recruit autologous or allogeneic natural killer (NK) cells in patients and trigger the elimination of AML-LSCs via antibody-dependent cellular cytotoxicity (ADCC).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3716745&req=5

Figure 1: Figure 1. Strategies to purge acute myeloid leukemia stem cells in autologous stem cell grafts and patients. (A) The depletion of acute myeloid leukemia (AML) leukemic stem cells (LSCs, red) from autologous hematopoietic progenitor cells (HPCs, blue) grafts in vitro may be achieved by means of a MicroBead-coupled antibody targeting an AML stem cell antigen and the magnetic-activated cell sorting (MACS) technology. (B) Chimeric antibodies carrying a human Fc portion and binding to an AML-specific antigen may recruit autologous or allogeneic natural killer (NK) cells in patients and trigger the elimination of AML-LSCs via antibody-dependent cellular cytotoxicity (ADCC).
Mentions: In this context, the discrimination of normal HSCs and residual AML-LSCs is a stringent prerequisite. While both AML-LSCs and HSCs are characterized by the surface expression of CD34 and the lack of CD38,1 other antigens including CD33, CD44, CD123, CD47 and CLL-1 seem to be preferentially expressed by AML-LSCs.6 The potential use of monoclonal antibodies specific for these markers is limited by their expression on other cell types, which may result in very severe side effects. CD96 (TACTILE) has originally been detected on AML-LSCs, and its expression was confirmed on the majority of AML blasts in 30% of patients.7,8 Importantly, the expression of CD96 on healthy HSCs is low or absent. In addition, CD96 is expressed by activated T and NK cells, where it may be involved in the adhesion between effector and tumor cells.9 Although the physiological functions of CD96 on AML-LSCs are actually unknown, it may contribute to their adhesion to the bone marrow compartment. On the basis of the CD96 expression pattern and properties, we selected CD96 for the development of antibody-based strategies for the depletion of AML-LSCs from autologous HPC grafts ex vivo and for the elimination of CD96+ cells in patients (Fig. 1).10

Bottom Line: The persistence of leukemic stem cells (LSCs) in acute myeloid leukemia (AML) patients receiving chemotherapy may be responsible for the high frequency of relapse.The selective elimination of CD96(+) AML-LSCs by means of CD96-specific monoclonal antibodies may be a promising therapeutic approach and revitalize autologous hematopoietic progenitor cell transplantation.

View Article: PubMed Central - PubMed

Affiliation: Division of Stem Cell Transplantation and Immunotherapy; 2nd Department of Medicine; Christian-Albrechts-University of Kiel; Kiel, Germany.

ABSTRACT
The persistence of leukemic stem cells (LSCs) in acute myeloid leukemia (AML) patients receiving chemotherapy may be responsible for the high frequency of relapse. The selective elimination of CD96(+) AML-LSCs by means of CD96-specific monoclonal antibodies may be a promising therapeutic approach and revitalize autologous hematopoietic progenitor cell transplantation.

No MeSH data available.


Related in: MedlinePlus