scholarly journals A bispecific antibody enhances cytokine-induced killer-mediated cytolysis of autologous acute myeloid leukemia cells

Blood ◽  
1993 ◽  
Vol 81 (5) ◽  
pp. 1333-1341 ◽  
Author(s):  
T Kaneko ◽  
Y Fusauchi ◽  
Y Kakui ◽  
M Masuda ◽  
M Akahoshi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Bispecific Antibody ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Autologous Bone Marrow Transplantation ◽  
Interleukin 2 ◽  
Colony Assay ◽  
Acute Myeloid

Abstract An anti-CD3 Fab' x anti-CD13 Fab' bispecific antibody (BsAb) was generated. This BsAb reacted with both CD3+ T cells and CD13+ acute myeloid leukemia (AML) cells. We investigated whether cytokine- stimulated peripheral blood mononuclear cells (PBMC) could lyse patient AML cells after addition of the BsAb. When interleukin-2 (IL-2)- stimulated PBMC were assayed for their cytotoxicity against 51Cr- labeled allogeneic and autologous CD13+ AML cells, their activity was markedly enhanced by the addition of the BsAb. PBMC stimulated with IL- 2 plus anti-CD3 monoclonal antibody (MoAb) showed higher proliferative ability and higher cytotoxicity if this was expressed as lytic units per culture. IL-7-stimulated PBMC also exhibited enhanced cytotoxicity against CD13+ AML cells after addition of the BsAb. Ultrastructurally, CD13+ AML cells incubated with IL-2 plus anti-CD3 MoAb-stimulated PBMC and the BsAb showed apoptotic morphologic changes. A colony assay for AML blast progenitors showed that the colony formation of CD13+ AML cells was inhibited by the addition of autologous IL-2 plus anti-CD3 MoAb-stimulated PBMC, and that this inhibition was further enhanced by the addition of the BsAb. A colony assay for normal bone marrow progenitor cells showed that the addition of autologous IL-2 plus anti- CD3 MoAb-stimulated PBMC and the BsAb inhibited the formation of granulocyte-macrophage colonies and mixed-cell colonies. However, the degree of inhibition was smaller than that for the AML blast colonies. Taken together, these findings suggest that this BsAb may be useful for ex vivo purging of CD13+ AML cells in autologous bone marrow transplantation.

scholarly journals A bispecific antibody enhances cytokine-induced killer-mediated cytolysis of autologous acute myeloid leukemia cells

Blood ◽  
1993 ◽  
Vol 81 (5) ◽  
pp. 1333-1341 ◽  
Author(s):  
T Kaneko ◽  
Y Fusauchi ◽  
Y Kakui ◽  
M Masuda ◽  
M Akahoshi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Bispecific Antibody ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Autologous Bone Marrow Transplantation ◽  
Interleukin 2 ◽  
Colony Assay ◽  
Acute Myeloid

An anti-CD3 Fab' x anti-CD13 Fab' bispecific antibody (BsAb) was generated. This BsAb reacted with both CD3+ T cells and CD13+ acute myeloid leukemia (AML) cells. We investigated whether cytokine- stimulated peripheral blood mononuclear cells (PBMC) could lyse patient AML cells after addition of the BsAb. When interleukin-2 (IL-2)- stimulated PBMC were assayed for their cytotoxicity against 51Cr- labeled allogeneic and autologous CD13+ AML cells, their activity was markedly enhanced by the addition of the BsAb. PBMC stimulated with IL- 2 plus anti-CD3 monoclonal antibody (MoAb) showed higher proliferative ability and higher cytotoxicity if this was expressed as lytic units per culture. IL-7-stimulated PBMC also exhibited enhanced cytotoxicity against CD13+ AML cells after addition of the BsAb. Ultrastructurally, CD13+ AML cells incubated with IL-2 plus anti-CD3 MoAb-stimulated PBMC and the BsAb showed apoptotic morphologic changes. A colony assay for AML blast progenitors showed that the colony formation of CD13+ AML cells was inhibited by the addition of autologous IL-2 plus anti-CD3 MoAb-stimulated PBMC, and that this inhibition was further enhanced by the addition of the BsAb. A colony assay for normal bone marrow progenitor cells showed that the addition of autologous IL-2 plus anti- CD3 MoAb-stimulated PBMC and the BsAb inhibited the formation of granulocyte-macrophage colonies and mixed-cell colonies. However, the degree of inhibition was smaller than that for the AML blast colonies. Taken together, these findings suggest that this BsAb may be useful for ex vivo purging of CD13+ AML cells in autologous bone marrow transplantation.

scholarly journals Bone marrow transplantation with interleukin-2-activated bone marrow followed by interleukin-2 therapy for acute myeloid leukemia in mice

Blood ◽  
1990 ◽  
Vol 76 (11) ◽  
pp. 2187-2190 ◽  
Author(s):  
BS Charak ◽  
RK Brynes ◽  
S Groshen ◽  
SC Chen ◽  
A Mazumder
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Myeloid Leukemia ◽  
Autologous Bone Marrow Transplantation ◽  
Interleukin 2 ◽  
Autologous Bone Marrow ◽  
Acute Myeloid

Abstract We have investigated approaches to induce graft-versus-leukemia (GVL) effect in autologous bone marrow transplantation (ABMT) without graft- versus-host disease to improve survival and cure in leukemia. The present study shows that bone marrow transplantation (BMT) using syngeneic bone marrow activated with interleukin-2 (ABM) for 24 hours in vitro, followed by interleukin-2 (IL-2) therapy, was superior to BMT with fresh, syngeneic bone marrow (FBM) in terms of survival and cure in mice with acute myeloid leukemia (P less than .001) and led to normal hematopoietic reconstitution. Addition of IL-2 therapy after BMT with FBM did not improve the results over BMT with FBM alone (P = .98). These results suggest that the GVL effect of ABMT can be enhanced by using ABM for BMT followed by IL-2 therapy without compromising engraftment.

scholarly journals Bone marrow transplantation with interleukin-2-activated bone marrow followed by interleukin-2 therapy for acute myeloid leukemia in mice

Blood ◽  
1990 ◽  
Vol 76 (11) ◽  
pp. 2187-2190 ◽  
Author(s):  
BS Charak ◽  
RK Brynes ◽  
S Groshen ◽  
SC Chen ◽  
A Mazumder
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Myeloid Leukemia ◽  
Autologous Bone Marrow Transplantation ◽  
Interleukin 2 ◽  
Autologous Bone Marrow ◽  
Acute Myeloid

We have investigated approaches to induce graft-versus-leukemia (GVL) effect in autologous bone marrow transplantation (ABMT) without graft- versus-host disease to improve survival and cure in leukemia. The present study shows that bone marrow transplantation (BMT) using syngeneic bone marrow activated with interleukin-2 (ABM) for 24 hours in vitro, followed by interleukin-2 (IL-2) therapy, was superior to BMT with fresh, syngeneic bone marrow (FBM) in terms of survival and cure in mice with acute myeloid leukemia (P less than .001) and led to normal hematopoietic reconstitution. Addition of IL-2 therapy after BMT with FBM did not improve the results over BMT with FBM alone (P = .98). These results suggest that the GVL effect of ABMT can be enhanced by using ABM for BMT followed by IL-2 therapy without compromising engraftment.

scholarly journals High-dose chemotherapy and autologous bone marrow transplantation in acute myeloid leukemia

Blood ◽  
1990 ◽  
Vol 76 (3) ◽  
pp. 480-488 ◽  
Author(s):  
AK McMillan ◽  
AH Goldstone ◽  
DC Linch ◽  
JG Gribben ◽  
KG Patterson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Matched Sibling ◽  
Autologous Bone ◽  
Acute Myeloid

Abstract For younger patients with acute myeloid leukemia (AML), an allogeneic transplant from a matched sibling may afford the best chance of cure. In patients who are older or without a matched sibling donor, dose intensification can be achieved with an autologous bone marrow transplant (ABMT). We report here the results of a high-dose chemotherapy regime with nonpurged ABMT in 82 adult patients in first remission of AML with a median follow-up of 31 months. The median age was 40 years (range 16 to 57 years). The median interval between remission and ABMT was 5 months (range 1 to 12 months). Twenty-eight of these patients received a second course of the same high-dose chemotherapy and ABMT. The procedure related mortality rate was 6%. The projected leukemia-free survival (LFS) at 5 years is 48% for all 82 patients and 50% for the 76 patients with no known preceding myelodysplastic syndrome. For those patients with primary AML who received a double ABMT the projected LFS is 67%. The interval between remission and ABMT did not predict for either relapse or LFS. ABMT using a multidrug chemotherapy protocol is less toxic than allogeneic BMT yet results in a similar LFS.

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