Immunologic control of a retrovirus-associated murine adenocarcinoma. VI. Augmentation of antibody-dependent killing following quantitative and qualitative changes in host peritoneal cells.

Attempts were made to augment the antibody-dependent killing of the ascitic AD755a tumor in vivo to protect C57BL/6J mice against the outgrowth of larger tumor burdens. The lethal dose for this tumor is less than 100 cells, and antibodies contained in a hyperimmune antitumor serum (HIS) were found to suppress the outgrowth of a maximum of about 5 X 10(5) cells. Thioglycollate injected ip increased the number of peritoneal macrophages, potential effectors for antibody-dependent cell-mediated cytotoxicity (ADCC), by tenfold to fortyfold and raised the maximum treatable tumor challenge (MTTC) to about 4 X 10(6) cells. By comparison, ip injection of Corynebacterium parvum increased the total peritoneal cell population by only twofold but raised the MTTC to about 20 X 10(6) cells. Neither agent alone had an effect on long-term survival, even at very low tumor inocula (1 X 10(3) cells). The protective HIS is known to contain tumor-binding antibodies in each of the IgG1, IgG2A, and IgG2B isotype fractions. Although the IgG2A fraction is far superior in vivo in the suppression of tumor outgrowth, the IgG2A fraction was also found to be most effective in combination with thioglycollate treatment in agreement with the observed preference of thioglycollate-elicited macrophages for this isotype in in vitro killing assays. In contrast following C. parvum treatment, all three isoptype fractions were equally suppressive to tumor outgrowth. A second major change following C. parvum treatment was that tumor cells precoated in vitro with antibodies were effectively eliminated in vivo. The same antibody-coated cells administered to thioglycollate-treated or unmanipulated animals were uniformly lethal even at much lower tumor doses. Taken together these results suggested a major qualitative change in the antibody-dependent tumor-killing process following C. parvum treatment. This change was most likely due to the C. parvum activation of highly lytic effector cells for ADCC, the identity of which was examined in an accompanying manuscript.