A bispecific antibody enhances cytokine-induced killer-mediated cytolysis
of autologous acute myeloid leukemia cells
T Kaneko, Y Fusauchi, Y Kakui, M Masuda, M Akahoshi, M Teramura, T Motoji, K Okumura, H Mizoguchi and K Oshimi
Department of Hematology, Tokyo Women's Medical College, Japan.
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.
Volume 81,
Issue 5,
pp. 1333-1341,
03/01/1993
Copyright © 1993 by The American Society of Hematology