A Therapeutic Antibody for Cancer, Derived from Single Human B Cells

Abstract

Summary: Some patients with cancer never develop metastasis, and their host response might provide cues for innovative treatment strategies. We previously reported an association between autoantibodies against complement factor H (CFH) and early-stage lung cancer. CFH prevents complement-mediated cytotoxicity (CDC) by inhibiting formation of cell-lytic membrane attack complexes on self-surfaces. In an effort to translate these findings into a biologic therapy for cancer, we isolated and expressed DNA sequences encoding high-affinity human CFH antibodies directly from single, sorted B cells obtained from patients with the antibody. The co-crystal structure of a CFH antibody-target complex shows a conformational change in the target relative to the native structure. This recombinant CFH antibody causes complement activation and release of anaphylatoxins, promotes CDC of tumor cell lines, and inhibits tumor growth in vivo. The isolation of anti-tumor antibodies derived from single human B cells represents an alternative paradigm in antibody drug discovery. : Bushey et al. clone antibodies against complement factor H (CFH) from single human B cells. CFH protects tumor cells from complement-dependent cytotoxicity (CDC). The authors demonstrate that a recombinant CFH antibody induces CDC of tumor cells, inhibits tumor growth in vivo, and stimulates infiltration of the tumor by lymphocytes.