Cooperation of IgG monoclonal antibodies in macrophage antibody-dependent cellular cytotoxicity (ADCC) to tumor targets.

Six IgG monoclonal antibodies representing the four murine IgG isotypes were active individually in ADCC to T-lymphoma targets mediated by murine macrophages and human blood K cells. The monoclonals were directed against four antigens (Thy-1.2, H-2k, Ly 2.1, Ly 9.2). None was as effective in ADCC as allo-anti-Thy-1.2 serum or rabbit anti-mouse spleen serum, even at plateau levels of killing. Monoclonals gave the highest levels of ADCC at relatively low amounts of antibody bound to targets; increasing the amount of bound antibody by 10- to 100-fold did not increase murine macrophage-mediated cytotoxicity. In contrast, ADCC using alloantiserum continued to increase over the same range of antibody bound to the tumor targets. The activity of individual monoclonals was not enhanced by the presence of various dilutions of normal mouse or rabbit serum, suggesting that the superiority of the allo- and hetero-antisera was due to their content of heterogeneous antibodies. IgG monoclonals of different isotypes and recognizing different antigens gave enhanced ADCC in combination; monoclonals to the same antigen did not. An IgM anti-Thy-1.2 monoclonal was inactive in ADCC and inhibited the activity of IgG monoclonals of the same specificity. These studies show that IgG antibodies of different specificity and class can collaborate in ADCC, and that this cooperative effect is not due simply to increased amounts of antibody bound to the tumor targets.