A Therapeutic Antibody for Cancer, Derived from Single Human B Cells.
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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.
Published Version (Please cite this version)10.1016/j.celrep.2016.04.038
Publication InfoAlam, S Munir; Bentley, RC; Bushey, RT; Campa, Michael Joseph; Gottlin, EB; Haynes, Barton Ford; ... Roy Choudhury, K (2016). A Therapeutic Antibody for Cancer, Derived from Single Human B Cells. Cell Rep, 15(7). pp. 1505-1513. 10.1016/j.celrep.2016.04.038. Retrieved from https://hdl.handle.net/10161/12221.
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Professor in Medicine
Research Interests. The Alam laboratory’s primary research is focused on understanding the biophysical properties of antigen-antibody binding and the molecular events of early B cell activation using the HIV-1 broadly neutralizing antibody (bnAb) lineage models. We are studying how HIV-1 Envelope proteins of varying affinities are sensed by B cells expressing HIV-1 bnAbs or their germline antigen receptors and initiate early signaling events for their activation. In the lon
Associate Professor in Radiology
There is longstanding evidence that invasive lung cancer is the end result of a multi-step process in which progressive molecular changes herald and accompany cytomorphologic changes. Our knowledge of these molecular events and the specific markers associated with the evolution from initiation to invasion is only partial. A number of specific biomarkers involved in oncogene activation or inactivation of tumor suppressor genes have been identified, but no single marker to date has been show
Frederic M. Hanes Professor of Medicine
The Haynes lab is studying host innate and adaptive immune responses to the human immunodeficiency virus (HIV), tuberculosis (TB), and influenza in order to find the enabling technology to make preventive vaccines against these three major infectious diseases. Mucosal Immune Responses in Acute HIV Infection The Haynes lab is working to determine why broadly neutralizing antibodies are rarely made in acute HIV infection (AHI), currently a major obstacle in the de
Professor in Neurosurgery
Brain Tumors, Preclinical Testing, Translational Research
Adjunct Professor in the Department of Medicine
Dr. Liao is a Professor of Medicine and Research Director of Duke Human Vaccine Institute. Dr. Liao is a MD virologistt rained in China. In early 1980’s, Dr. Liao made major contributions to the first isolation of epidemic hemorrhagic fever virus (hataanvirus) from Apodemus agraius using tissue culture in China. The successful identification and isolation of Hataanvirus enabled the early diagnosis and treatment of the disease, and advancement of HFRS research towards prevention by de
Adjunct Associate Professor in the Department of Biostatistics and Bioinformatics
Statistical modelling, data analysis. Analysis of multiple observer studies. Analysis of complex data. Modelling tumor growth. Translation in drug discovery.Statistical analysis of images: cellular and medical imaging. Statistics of shape, structure and spatial arrangement.
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