SELECTION OF RECOMBINANT ANTI-HUD FAB FRAGMENTS FROM A PHAGE DISPLAY ANTIBODY LIBRARY OF A LUNG-CANCER PATIENT WITH PARANEOPLASTIC ENCEPHALOMYELITIS

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 e ncephalomyelitis and sensory neuropathy (PEM/SN). We isolated anti-HuD Fab fragments from an antibody phage display library that was constru cted 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-Nl. or Hu antigens) in immunoblots of these recombinant proteins and in immunohistochemical and Western blot analysis of SCLC and neuro ns. Fab GLN495 inhibited up to 75% of the anti-Hu antibodies of the pa tient from which it was derived, suggesting that it recognizes a domin ant epitope in the polyclonal anti-Hu antibody response. Fab GLN495 al so 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 di agnosis of HuD expressing tumors and in clarifying the autoimmune etio logy of PEM/SN. This study, the first to demonstrate that tumor specif ic recombinant antibodies can be isolated from metastatic lymph node t issue. shows that this approach may be generally applicable to isolate human antibodies against tumor specific antigens. (C) 1998 Elsevier S cience B.V.