An in vivo model of human CD20+ B-lymphoma was
established in severe combined immunodeficiency mice to
test the ability of human neutralizing miniantibodies to CD55
and CD59 (MB55 and MB59) to enhance the therapeutic effect
of rituximab. The miniantibodies contained single-chain
fragment variables and the hinge-CH2-CH3 domains of human
IgG1. LCL2 cells were selected for the in vivo study among
six B-lymphoma cell lines for their high susceptibility to
rituximab-dependent complement-mediated killing enhanced
by MB55 and MB59. The cells injected i.p. primarily colonized
the liver and spleen, leading to the death of the animals within
30 to 40 days. Thirty percent of mice receiving biotin-labeled
rituximab (25 Mg) i.p. on days 4 and 11 after cell injection
survived to 120 days. Administration of biotin-labeled
rituximab, followed by avidin (40 Mg) and biotin-labeled
MB55–MB59 (100 Mg) at 4-h intervals after each injection
resulted in the survival of 70% of mice. Surprisingly, 40%
of mice survived after the sole injection of avidin and biotin-
labeled MB55–MB59, an observation consistent with the
in vitro data showing that the miniantibodies induced killing
of f25% cells through antibody-dependent cell cytotoxicity.
In conclusion, MB55 and MB59 targeted to tumor cells
represent a valuable tool to enhance the therapeutic effect
of rituximab and other complement-fixing antitumor anti-
bodies.
