Br. Wei et al., The combined use of an immunotoxin and a radioimmunoconjugate to treat disseminated human B-cell lymphoma in immunodeficient mice, CLIN CANC R, 6(2), 2000, pp. 631-642
Immunoconjugates (ICs) consist of a targeting moiety and a toxic moiety and
have the specificity that traditional cancer therapy lacks. At appropriate
doses, ICs are safe and effective in treating various cancers in experimen
tal animals and in humans. However, because cures are rarefy achieved using
single agents, regimens involving combinations of agents with different me
chanisms of action must be evaluated. In this study, we explored the effica
cy and toxicity of a combination of two IC therapies, radioimmunotherapy (R
IT) and immunotoxin (IT) therapy, to treat advanced, disseminated human lym
phoma in immunodeficient mice. We proposed to use the bystander effect of R
IT to reduce large tumor burdens, followed by an IT to eliminate residual t
umor cells. Our results indicate that, when used alone, both RIT and IT the
rapy were safe and effective, but not curative. When the two therapies were
combined, efficacy and toxicity became dependent on the temporal order of
administration. Thus, with the doses used in this study, when RIT was admin
istered after IT therapy, the regimen,vas curative. In contrast, when RIT w
as administered before IT therapy, the combination was highly toxic or even
lethal. Both RIT and IT therapy induced pulmonary vascular leak,but with d
ifferent kinetics. When RIT was given prior to IT therapy, the pulmonary va
scular leak became life-threatening but not when the two agents were admini
stered in the reverse order.