A Therapeutic Antibody for Cancer, Derived from Single Human B Cells
Ryan T. Bushey,
M. Anthony Moody,
Nathan L. Nicely,
Barton F. Haynes,
S. Munir Alam,
Stephen T. Keir,
Rex C. Bentley,
Kingshuk Roy Choudhury,
Elizabeth B. Gottlin,
Michael J. Campa,
Hua-Xin Liao,
Edward F. Patz, Jr.
Affiliations
Ryan T. Bushey
Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA
M. Anthony Moody
Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA; Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA; Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA
Nathan L. Nicely
Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA
Barton F. Haynes
Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA; Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA; Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
S. Munir Alam
Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA
Stephen T. Keir
Department of Neurosurgery, Duke University Medical Center, Durham, NC 27710, USA
Rex C. Bentley
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
Kingshuk Roy Choudhury
Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA; Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC 27710, USA
Elizabeth B. Gottlin
Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA
Michael J. Campa
Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA
Hua-Xin Liao
Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA; Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA; Corresponding author
Edward F. Patz, Jr.
Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA; Corresponding author
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.
