COMPLEMENT-MEDIATED KILLING OF MICROTUMORS IN-VITRO

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.