Depletion of the C3 component of complement enhances the ability of rituximab-coated target cells to activate human NK cells and improves the efficacy of monoclonal antibody therapy in an in vivo model

The dual role of complement in cancer and its implication in anti-tumor therapy

“…Wang et al have shown, both in vitro (125) and in vivo (126), that complement components can impede the efficiency of rituximab by inhibiting the ability of rituximab-coated targets to induce NK cell activation. They concluded that C1q and C3 presence in the serum was required for these inhibitory effects, while C5 was not involved.…”

Regulation of complement and modulation of its activity in monoclonal antibody therapy of cancer

“…In the syngeneic mouse model, mice depleted of complement showed an improved antitumor effect. 74 It has also been observed that patients homozygous for a SNP in the C1qA gene that results in lower C1q levels (Gly70GGA) achieved a prolonged remission when treated with rituximab monotherapy compared with heterozygous or homozygous G genotyped patients (Gly70GGG). 75 Taken together, in vitro complement activation by mAbs is well supported, yet the relative importance of complement to the anti-tumor effect is unclear.…”

Transient Complement Inhibition Promotes a Tumor-Specific Immune Response through the Implication of Natural Killer Cells

“…25). Furthermore, the depletion of complement has been shown to enhance the survival rates following mAb therapy in a syngeneic mouse model of lymphoma (26). To ascertain whether the enhanced tumor control in the decomplemented mice was a direct consequence of the increased proportions of NK cells, we depleted NK cells 4 days after tumor implantation.…”