5EA0

Structure of the antibody 7968 with human complement factor H-derived peptide

Summary for 5EA0

• Entry DOI: 10.2210/pdb5ea0/pdb
• Descriptor: Heavy chain of antibody 7968 Fab fragment, Light chain of antibody 7968 Fab fragment, Complement factor H-related protein 2, ... (4 entities in total)
• Functional Keywords: complement factor h cfh scr19 scr19-20, immune system
• Biological source: Homo sapiens; More
• Cellular location: Secreted: P36980
• Total number of polymer chains: 3
• Total formula weight: 49355.16

Authors

Bushey, R.T.,Moody, M.A.,Nicely, N.I.,Alam, S.M.,Haynes, B.F.,Winkler, M.T.,Gottlin, E.B.,Campa, M.J.,Liao, H.-X.,Patz Jr., E.F. (deposition date: 2015-10-15, release date: 2016-05-25, Last modification date: 2024-11-06)

Primary citation

Bushey, R.T.,Moody, M.A.,Nicely, N.L.,Haynes, B.F.,Alam, S.M.,Keir, S.T.,Bentley, R.C.,Roy Choudhury, K.,Gottlin, E.B.,Campa, M.J.,Liao, H.X.,Patz, E.F.
A Therapeutic Antibody for Cancer, Derived from Single Human B Cells.
Cell Rep, 15:1505-1513, 2016

PubMed Abstract: 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.

PubMed: 27160908
DOI: 10.1016/j.celrep.2016.04.038

Experimental method

X-RAY DIFFRACTION (2 Å)