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

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.

Authors:
; ; ; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES); LUNGevity Foundation, the Dept. of Defense; National Institutes of Health (NIH)
OSTI Identifier:
1325319
Alternate Identifier(s):
OSTI ID: 1256369
Grant/Contract Number:  
W-31-109-Eng-38; W81XWH-13-1-0189; UL1TR001117
Resource Type:
Published Article
Journal Name:
Cell Reports
Additional Journal Information:
Journal Name: Cell Reports Journal Volume: 15 Journal Issue: 7; Journal ID: ISSN 2211-1247
Publisher:
Elsevier
Country of Publication:
Netherlands
Language:
English
Subject:
60 APPLIED LIFE SCIENCES

Citation Formats

Bushey, Ryan T., Moody, M. Anthony, Nicely, Nathan L., Haynes, Barton F., Alam, S. Munir, Keir, Stephen T., Bentley, Rex C., Roy Choudhury, Kingshuk, Gottlin, Elizabeth B., Campa, Michael J., Liao, Hua-Xin, and Patz, Jr., Edward F. A Therapeutic Antibody for Cancer, Derived from Single Human B Cells. Netherlands: N. p., 2016. Web. https://doi.org/10.1016/j.celrep.2016.04.038.
Bushey, Ryan T., Moody, M. Anthony, Nicely, Nathan L., Haynes, Barton F., Alam, S. Munir, Keir, Stephen T., Bentley, Rex C., Roy Choudhury, Kingshuk, Gottlin, Elizabeth B., Campa, Michael J., Liao, Hua-Xin, & Patz, Jr., Edward F. A Therapeutic Antibody for Cancer, Derived from Single Human B Cells. Netherlands. https://doi.org/10.1016/j.celrep.2016.04.038
Bushey, Ryan T., Moody, M. Anthony, Nicely, Nathan L., Haynes, Barton F., Alam, S. Munir, Keir, Stephen T., Bentley, Rex C., Roy Choudhury, Kingshuk, Gottlin, Elizabeth B., Campa, Michael J., Liao, Hua-Xin, and Patz, Jr., Edward F. Sun . "A Therapeutic Antibody for Cancer, Derived from Single Human B Cells". Netherlands. https://doi.org/10.1016/j.celrep.2016.04.038.
@article{osti_1325319,
title = {A Therapeutic Antibody for Cancer, Derived from Single Human B Cells},
author = {Bushey, Ryan T. and Moody, M. Anthony and Nicely, Nathan L. and Haynes, Barton F. and Alam, S. Munir and Keir, Stephen T. and Bentley, Rex C. and Roy Choudhury, Kingshuk and Gottlin, Elizabeth B. and Campa, Michael J. and Liao, Hua-Xin and Patz, Jr., Edward F.},
abstractNote = {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.},
doi = {10.1016/j.celrep.2016.04.038},
journal = {Cell Reports},
number = 7,
volume = 15,
place = {Netherlands},
year = {2016},
month = {5}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1016/j.celrep.2016.04.038

Citation Metrics:
Cited by: 4 works
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