BISPECIFIC MONOCLONAL-ANTIBODY DIRECTED AGAINST BOTH THE MEMBRANE-BOUND COMPLEMENT REGULATOR CD55 AND THE RENAL TUMOR-ASSOCIATED ANTIGEN G250 ENHANCES C3 DEPOSITION AND TUMOR-CELL LYSIS BY COMPLEMENT
Vt. Blok et al., BISPECIFIC MONOCLONAL-ANTIBODY DIRECTED AGAINST BOTH THE MEMBRANE-BOUND COMPLEMENT REGULATOR CD55 AND THE RENAL TUMOR-ASSOCIATED ANTIGEN G250 ENHANCES C3 DEPOSITION AND TUMOR-CELL LYSIS BY COMPLEMENT, The Journal of immunology, 160(7), 1998, pp. 3437-3443
Tumor cells may inhibit the induction of a complement-mediated inflamm
atory response through overexpression of membrane-bound regulators of
complement activation, Therefore, it is of interest to determine the m
ost efficient approach to block these membrane-bound complement regula
tors on tumor cells, In the present study, we first generated a bispec
ific mAb directed against both CD55, using the functional blocking mAb
MBC1, and the highly expressed HLA class I molecule as a model for a
tumor-associated Ag, using the mAb W6/32, Tumor cells opsonized with b
ispecific mAb W6/32MBC1, then exposed to complement and subsequently
stained for C3 deposition, were assessed by how cytometric analysis, W
e found that opsonization with W6/32MBC1 resulted in a 92% enhancemen
t of C3 deposition on renal tumor cells as compared with opsonization
with W6/32 alone and a 17% enhancement of the C3 deposition as compare
d with incubation with a mixture of both parental mAb, Based on these
results, we developed a bispecific mAb recognizing both CD55 and the r
elatively low expressed renal tumor-associated Ag G250. Increasing con
centrations of the bispecific mAb G250MBC1 resulted in a 25 to 400% i
ncrease in C3 deposition on;renal tumor cells as compared with C3 depo
sition in the presence of the parental mAb G250 alone, G250MBC1 enhan
ced C3 deposition by 21% in comparison with a mixture of both parental
s, Furthermore, opsonization of tumor cells with G250MBC1 rendered th
ese cells more sensitive to complement-mediated lysis, In conclusion,
the bispecific mAb G250MBC1 induces deposition of C3 and tumor cell l
ysis more efficiently than G250 alone.