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G19.4(alpha CD3) x B43(alpha CD19) monoclonal antibody heteroconjugate
triggers CD19 antigen-specific lysis of t(4;11) acute lymphoblastic
leukemia cells by activated CD3 antigen-positive cytotoxic T cells
PM Anderson, W Crist, D Hasz, AJ Carroll, DE Myers and FM Uckun
Department of Pediatrics, University of Minnesota, Minneapolis.
A highly purified, 300-Kd bispecific monoclonal antibody (MoAb)
heteroconjugate was prepared by covalently linking the anti-CD3 MoAb,
G19.4, to the anti-CD19 MoAb, B43. Dual-color staining techniques and
multiparameter flow cytometry confirmed that this alpha CD3 x alpha CD19
heteroconjugate was able to bind to both CD3+ T cells and CD19+ t(4;11)
acute lymphoblastic leukemia (ALL) cells. T-cell-mediated lysis of freshly
isolated primary bone marrow blasts from nine newly diagnosed ALL patients
with a t(4;11)(q21;q23) chromosomal translocation were studied with
51Cr-release assays. Picomolar concentrations of alpha CD3 x alpha CD19
MoAb heteroconjugate effectively triggered lysis of CD19+ t(4;11) ALL cells
by interleukin-2- activated CD3+ peripheral blood T-cell (PBTC) effectors
but did not augment the cytolytic activity of the same effectors against
CD19- T- ALL cells. In contrast to the alpha CD3 x alpha CD19
heteroconjugate, neither the alpha CD3 x alpha CD3 homoconjugate control
nor the alpha CD19 x alpha CD72 heteroconjugate control facilitated the
cytolysis of t(4;11) ALL blasts. Occupation of the target CD19 binding
sites on t(4;11) ALL blasts by preincubation with excess unconjugated alpha
CD19 MoAb abrogated the potentiating effects of the alpha CD3 x alpha CD19
heteroconjugate on PBTC-mediated cytolysis. Thus, the cell type- specific
cytolysis of t(4;11) ALL blasts by PBTC effectors is dependent on both the
alpha CD19 and alpha CD3 moieties of the alpha CD3 x alpha CD19
heteroconjugate. To our knowledge, this is the first description of an
effective bispecific antibody that facilitates the T-cell- mediated lysis
of t(4;11) ALL blasts.
Volume 80,
Issue 11,
pp. 2826-2834,
12/01/1992
Copyright © 1992 by The American Society of Hematology
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