Extremely potent, rapid and costimulation-independent cytotoxic T-cell response against XXXX cells catalyzed by a single-chain bispecific antibody.

@entity1 @entity404 @entity706 @entity1075 @entity2225 @entity1892 @entity1199 @entity405
A recent study reported on an anti- @entity1075 /anti-CD3 single-chain bispecific antibody (bscCD19xCD3) exhibiting high activity against @entity1 @entity1892 cell lines (L  ffler et al., Blood 2000;95:2098-103). In the present study, we have explored in detail the in vitro efficacy, T-cell donor variability, binding characteristics, specificity, kinetics and @entity1199 ( @entity1199 ) dependence of bscCD19xCD3. We found that a majority of @entity1 donor T cells tested (n = 86) gave half-maximal B- @entity706 cell lysis (ED(50)) within a range of 10-50 pg/ml bscCD19xCD3, corresponding to sub-picomolar concentrations of the bispecific antibody. Under identical experimental conditions, the anti- @entity2225 monoclonal antibody rituximab had an at least 100,000-fold lower in vitro efficacy. The extreme potency of bscCD19xCD3 was in sharp contrast to the relatively low affinity of the anti-CD3 and anti- @entity1075 single-chain Fv portions in K(D) ranges of 10(-7) and 10(-9) M, respectively. Cell lysis by bscCD19xCD3 was predominantly mediated by the population of @entity405 /CD45RO-positive T cells. Both immortalized @entity404 - and @entity405 -positive @entity1 T-cell clones were highly active effector cells as well. Cell lysis by bscCD19xCD3 was rapid and specific. The respective parental monoclonal antibodies inhibited cell lysis and @entity1075 -negative cells were not harmed by T cells in the presence of high amounts of bscCD19xCD3. The potent T-cell stimulus @entity1199 could not markedly augment the activity of bscCD19xCD3-stimulated T cells. In conclusion, bscCD19xCD3 could redirect unstimulated cytotoxic T cells against @entity1075 -positive cells in an unexpectedly potent, rapid and specific fashion.
