Enhancement of complement-mediated antitumor antibody mechanisms by CR2-Fc. Antitumor antibodies bound to tumor antigens (1) activate the complement system leading to the deposition of activated C3 fragments. (2) These fragments may further activate the complement cascade eventually leading to tumor cell lysis via the formation of the membrane attack complex. Complement fragments can be recognized by complement receptors expressed on effector cells leading to direct cytotoxicity or enhanced FcR-dependent tumor killing. The CR2-Fc fusion protein targets deposited C3 fragments on the tumor cells, (3) activates complement, and generates its own ligand, thereby amplifying complement activation. (4) In addition, CR2-Fc binding increases the available Fc fragments leading to enhanced Fc receptor-mediated tumor killing. Professional illustration by Paulette Dennis.