Complement-mediated lysis of cancer cells growing in three-dimensional
aggregates involves factors that are not associated with the killing
of cells in suspension. We have used multicellular tumor spheroids est
ablished from breast carcinoma (T47D) and ovarian teratocarcinoma (PA-
1) cell lines as models to study complement-mediated destruction of mi
crometastases and small solid tumors. We found that significant killin
g of microtumors treated with an antitumor antibody and a specific mon
oclonal antibody (YTH53.1) against the complement lysis inhibitor prot
ectin (CD59) started to occur after a 1 to 2-hour lag phase. After an
overnight incubation, the microtumors became totally infiltrated by th
e YTH53.1 monoclonal antibody and C1q, whereas C3 and C5b-9 penetrated
as a frontier to the peripheral cell layers. A Cr-51 release assay sh
owed that during a 24-hour pulsed treatment with complement, 33% of ce
lls in the spheroids were killed, and the average tumor volume decreas
ed by 28%. According to propidium iodide staining, complement exposure
resulted in killing and peeling off of the outermost tumor cells.