Complement activation by mAbs can cause direct tumor cell lysis or enhance antibody-dependent cell-mediated cytotoxicity. However, tumor cells are protected from complement-mediated injury by membrane-bound complement regulatory proteins (mCRP) that are often expressed at elevated levels on tumor cells. Recent studies indicate that blocking or over-whelming the function of tumor cell mCRP might substantially improve the efficacy of monoclonal antibody (mAb) immunotherapy. In addition, the use of b-glucan as an adjuvant for mAb immunotherapy enables iC3b deposited on tumor cells by mAbs to activate complement receptor 3 (CR3) on effector cells, thus inducing CR3-dependent cellular cytotoxicity. These strategies provide novel cell-mediated mechanisms of tumor cytotoxicity that are additive to all other mAb effector mechanisms.