This technology includes a strategy to target tumor cells that lost antigen following reaction with a therapeutic antibody by targeting the complement component C3d that has been deposited on target cells by the primary antibody. We previously generated a C3d-specific mouse/human chimeric antibody called C8xi and obtained proof of principle for the approach in two preclinical models. Here we summarize the generation of a new set of C3d targeting antibodies. We obtained several rabbit/ chimeric antibodies, some of these antibodies bind both human and mouse C3d; having different sequences and binding epitopes than C8xi. Two mouse C3d reactive antibodies were tested in an aggressive lymphoma model and synergized with anti-CD20 antibodies.