Selection of recombinant anti-HuD Fab fragments from a phage display antibody library of a lung cancer patient with paraneoplastic encephalomyelitis Journal Article

  


Authors: Graus, Y. F.; Verschuuren, J. J.; Degenhardt, A.; van Breda Vriesman, P. J.; De Baets, M. H.; Posner, J. B.; Burton, D. R.; Dalmau, J.
Article Title: Selection of recombinant anti-HuD Fab fragments from a phage display antibody library of a lung cancer patient with paraneoplastic encephalomyelitis
Abstract: Antibodies against the HuD antigen expressed in small-cell lung cancer (SCLC) cross-react with proteins expressed in neurons of the central and peripheral nervous system and are associated with paraneoplastic encephalomyelitis and sensory neuropathy (PEM/SN). We isolated anti-HuD Fab fragments from an antibody phage display library that was constructed from mRNA of a metastatic lymph node from a patient with SCLC and PEM/SN. Fab GLN495 recognized HuD and other related proteins (HuC and Hel-N1, or Hu antigens) in immunoblots of these recombinant proteins and in immunohistochemical and Western blot analysis of SCLC and neurons. Fab GLN495 inhibited up to 75% of the anti-Hu antibodies of the patient from which it was derived, suggesting that it recognizes a dominant epitope in the polyclonal anti-Hu antibody response. Fab GLN495 also competed with anti-Hu sera from most but not all patients with PEM/SN, indicating that the same epitope is recognized by a large subgroup of patients. Human monoclonal anti- HuD antibodies may be useful in diagnosis of HuD expressing tumors and in clarifying the autoimmune etiology of PEM/SN. This study, the first to demonstrate that tumor specific recombinant antibodies can be isolated from metastatic lymph node tissue, shows that this approach may be generally applicable to isolate human antibodies against tumor specific antigens.
Keywords: controlled study; human tissue; unclassified drug; gene deletion; lymph node metastasis; antigen expression; sensory neuropathy; lung neoplasms; nerve tissue proteins; neurons; tumor antigen; rna-binding proteins; lung small cell cancer; amino acid sequence; molecular sequence data; antibody response; antigen recognition; recombinant proteins; recombinant protein; autoimmunity; antibodies; paraneoplastic syndrome; hu antigen; hu paraneoplastic encephalomyelitis antigens; phage display; carcinoma, small cell; epitopes; immunoglobulin f(ab) fragment; encephalomyelitis; paraneoplastic syndromes; bacteriophages; human antibody; immunoglobulin fab fragments; cross reacting antibody; humans; human; priority journal; article; hud; hu d antigen
Journal Title: Journal of Neuroimmunology
Volume: 82
Issue: 2
ISSN: 0165-5728
Publisher: Elsevier Inc.  
Date Published: 1998-03-01
Start Page: 200
End Page: 209
Language: English
DOI: 10.1016/s0165-5728(97)00199-9
PUBMED: 9585817
PROVIDER: scopus
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-0031917261&doi=10.1016%2fS0165-5728%2897%2900199-9&partnerID=40&md5=595366d3611ae8c50e54f4b6bb17bd57
Notes: Article -- Export Date: 12 December 2016 -- Source: Scopus
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MSK Authors
  1. Jerome B Posner
    211 Posner
  2. Josep O Dalmau
    101 Dalmau
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