Antibody and complement modulation of tumor cell growth in vitro and in vivo.

Low doses of highly purified anti-TNP (trinitrophenyl) antibody specifically stimulated nucleoside uptake in TNP-substituted L cells and low doses of heterospecific anti-L cell antibody stimulated nucleoside incorporation, DNA synthesis, and cell growth in L cells in vitro. High concentrations of antibody inhibited these processes. Complement activated through C3 augmented the cytostimulatory effects of low concentrations of antibody and activated through C9 augmented the cytoinhibitory effects of antibody. One very early effect of cytostimulatory concentrations of antibody is activation of membrane carrier transport systems as seen with 45Ca2+ uptake. Growth of L cells in tissue culture in the continuous presence of a cytostimulatory concentration of antibody selected for a variant cell line that was less responsive to antibody, thought to be due to a blocking effect of increased amounts of sialic acid. In vivo experiments documented that the same antibody could modulate L cell tumor growth in T cell-depleted mice, depending on whether a low or high concentration of antibody was given passively. In the experimental systems used, therefore, antitumor antibody and complement directly modulate the growth of tumor cells.