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.