Removal of acute lymphoblastic leukemia (ALL) cells from human bone marrow using monoclonal antibodies (MoAbs) and complement - A review

Author(s):  
P HERVE ◽  
E RACADOT
Blood ◽  
1984 ◽  
Vol 64 (3) ◽  
pp. 662-666
Author(s):  
P Hokland ◽  
LM Nadler ◽  
JD Griffin ◽  
SF Schlossman ◽  
J Ritz

Mononuclear cells expressing the common acute lymphoblastic leukemia antigen (CALLA) were purified from normal adult human bone marrow, where they constitute a small fraction of the total population. This was accomplished by a two-step purification from Ficoll-Hypaque- isolated mononuclear cells. Isolated mononuclear cells were first labeled with a mixture of monoclonal antibodies (MoAb) specific for myeloid and erythroid precursor cells, and immune rosettes were then formed with sheep erythrocytes coated with rabbit anti-mouse antibodies (R/M-SRBC). Sedimentation through Ficoll-Hypaque then eliminated the majority of mature myeloid cells. The second step consisted of labeling the remaining rosette-negative cells with CALLA-specific MoAb and purifying CALLA+ cells by fluorescence activated cell sorting. Alternatively, CALLA+ cells were purified in a second R/M-SRBC rosette sedimentation step. The purified CALLA+ cells, which morphologically were medium to large lymphoid cells, were subsequently studied using dual fluorescence techniques to identify surface markers as well as intracytoplasmic staining to detect terminal deoxynucleotidyl transferase enzyme (TdT) and intracytoplasmic mu. While the CALLA+ cell suspensions contained very few mature myeloid cells or T lymphocytes, the finding that 5% to 11% of them were cyto-mu+ and 13% to 22% expressed the B1 differentiation antigen clearly indicated that at least some of these cells were B cell precursors. Because 48% to 63% of the cells were TdT+ and practically all of them expressed Ia antigen, it appears that these cells are a mixture of very early lymphoid precursor cells as well as more differentiated pre-B cells. The phenotype of these normal cells is very similar to that of common ALL cells. Differences in the surface marker phenotypes between adult and fetal CALLA+ cells that have previously been purified were also identified.


1995 ◽  
Vol 1 (1) ◽  
pp. 32-37 ◽  
Author(s):  
Meng Y Wang ◽  
Øystein Fodstad ◽  
Wolf-Dieter Ludwig ◽  
Mats Bengtsson ◽  
Thomas Totterman ◽  
...  

Blood ◽  
1984 ◽  
Vol 64 (3) ◽  
pp. 662-666 ◽  
Author(s):  
P Hokland ◽  
LM Nadler ◽  
JD Griffin ◽  
SF Schlossman ◽  
J Ritz

Abstract Mononuclear cells expressing the common acute lymphoblastic leukemia antigen (CALLA) were purified from normal adult human bone marrow, where they constitute a small fraction of the total population. This was accomplished by a two-step purification from Ficoll-Hypaque- isolated mononuclear cells. Isolated mononuclear cells were first labeled with a mixture of monoclonal antibodies (MoAb) specific for myeloid and erythroid precursor cells, and immune rosettes were then formed with sheep erythrocytes coated with rabbit anti-mouse antibodies (R/M-SRBC). Sedimentation through Ficoll-Hypaque then eliminated the majority of mature myeloid cells. The second step consisted of labeling the remaining rosette-negative cells with CALLA-specific MoAb and purifying CALLA+ cells by fluorescence activated cell sorting. Alternatively, CALLA+ cells were purified in a second R/M-SRBC rosette sedimentation step. The purified CALLA+ cells, which morphologically were medium to large lymphoid cells, were subsequently studied using dual fluorescence techniques to identify surface markers as well as intracytoplasmic staining to detect terminal deoxynucleotidyl transferase enzyme (TdT) and intracytoplasmic mu. While the CALLA+ cell suspensions contained very few mature myeloid cells or T lymphocytes, the finding that 5% to 11% of them were cyto-mu+ and 13% to 22% expressed the B1 differentiation antigen clearly indicated that at least some of these cells were B cell precursors. Because 48% to 63% of the cells were TdT+ and practically all of them expressed Ia antigen, it appears that these cells are a mixture of very early lymphoid precursor cells as well as more differentiated pre-B cells. The phenotype of these normal cells is very similar to that of common ALL cells. Differences in the surface marker phenotypes between adult and fetal CALLA+ cells that have previously been purified were also identified.


Science ◽  
1983 ◽  
Vol 222 (4623) ◽  
pp. 512-515 ◽  
Author(s):  
D. Vallera ◽  
R. Ash ◽  
E. Zanjani ◽  
J. Kersey ◽  
T. LeBien ◽  
...  

Blood ◽  
1985 ◽  
Vol 66 (3) ◽  
pp. 508-513 ◽  
Author(s):  
N Ramsay ◽  
T LeBien ◽  
M Nesbit ◽  
P McGlave ◽  
D Weisdorf ◽  
...  

Abstract Autologous bone marrow transplantation (BMT) was utilized as therapy for 23 patients with acute lymphoblastic leukemia (ALL) in second or greater remission. Bone marrow was treated in vitro with a combination of monoclonal antibodies, consisting of BA-1, BA-2, BA-3, and baby rabbit complement (BRC'). All patients were prepared for transplantation with cyclophosphamide and fractionated total body irradiation. Engraftment occurred in all 23 patients. Seven of 23 patients remain relapse-free from six to 32 months (median, 21.4 months) posttransplant. Failures were due to relapse with the exception of one patient who died of infection. This study demonstrates that autologous BMT using in vitro marrow treatment with BA-1, BA-2, BA-3, and BRC' is safe, allows engraftment, and results in prolonged survival for some patients with ALL in second or greater remission.


Blood ◽  
1993 ◽  
Vol 81 (7) ◽  
pp. 1819-1826 ◽  
Author(s):  
A Shibuya ◽  
H Kojima ◽  
K Shibuya ◽  
K Nagayoshi ◽  
T Nagasawa ◽  
...  

Natural killer (NK) cells can be cultured in interleukin-2 (IL-2)- containing medium from selected human bone marrow (BM) cells obtained after the elimination of mature T and NK cells. To isolate and characterize IL-2-responsive NK progenitors in the selected BM cells, we investigated the expression of IL-2 receptors (IL-2R) on these cells. Neither CD25 (IL-2R alpha) nor IL-2R beta antigen was observed on the selected BM cells before culture. However, CD25+ cells without detectable levels of IL-2R beta antigen appeared 24 hours after culture in IL-2-containing medium. Cells were sorted from each fraction of the selected BM cells 24 hours after culture after staining with anti-CD33, anti-CD34, and anti-CD25 monoclonal antibodies. The generation of NK cells (CD3- CD56+ cells) and NK activity were observed only from the CD33-/CD34-/CD25+ cell fraction after culture in IL-2-containing medium. The frequency of IL-2-responsive NK progenitors relative to the fraction was 1/231 (95% confidence range, 1/156 to 1/289), which corresponded to the frequency relative to the total number of selected BM cells when the frequency relative to the CD33-/CD34-/CD25+ cell- fraction was converted according to the percentage of these cells in the total number of selected BM cells. These results indicated that IL- 2-responsive NK progenitors were enriched in the CD33-/CD34-/CD25+ cell fraction.


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