title: Intratumoral anti-HuD immunotoxin therapy for small cell lung cancer and neuroblastoma.
abstract: BACKGROUND
  Most patients with small cell lung cancer (SCLC) or neuroblastoma (NB) already show clinically detectable metastases at diagnosis and have an extremely poor prognosis even when treated with combined modalities. The HuD-antigen is a neuronal RNA-binding protein that is expressed in 100% of SCLC tumor cells and over 50% of neuroblastoma cells. The correlation between high titers of circulating anti-HuD antibodies in patients and spontaneous tumor remission suggests that the HuD-antigen might be a potential molecular target for immunotherapy.
  
  
  METHODS
  We have constructed a new antibody-toxin compound (called BW-2) by assembling a mouse anti-human-HuD monoclonal antibody onto streptavidin/saporin complexes.
  
  
  RESULTS
  We found that the immunotoxin BW-2 specifically killed HuD-positive human SCLC and NB cancer cells at very low concentrations in vitro. Moreover, intratumoral immunotoxin therapy in a nude mouse model of human SCLC (n = 6) significantly reduced local tumor progression without causing toxicity. When the same intratumoral immunotoxin protocol was applied to an immunocompetent A/J mouse model of NB, significant inhibition of local tumor growth was also observed. In neuroblastoma allografted A/J mice (n = 5) treated twice with intratumoral immunotoxin, significant tumor regression occurred in over 80% of the animals and their duration of tumor response was significantly prolonged.
  
  
  CONCLUSIONS
  Our study suggests that anti-HuD based immunotoxin therapy may prove to be an effective alternative treatment for patients with SCLC and NB.
authors.affiliation: Department of Neurology and Neurosciences, Rutgers NJMS, Newark, NJ, USA. dehrlich88@gmail.com.
authors.forename: Debra
authors.initials: D
authors.lastname: Ehrlich
authors.affiliation: Department of Neurology and Neurosciences, Rutgers NJMS, Newark, NJ, USA. bo.wang@med.einstein.yu.edu.|Neurology Service, VA Medical Center, East Orange, NJ, USA. bo.wang@med.einstein.yu.edu.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Neurology Service, VA Medical Center, East Orange, NJ, USA. ludeer113@gmail.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: Neurology Service, VA Medical Center, East Orange, NJ, USA. dowlinpc@njms.rutgers.edu.
authors.forename: Peter
authors.initials: P
authors.lastname: Dowling
authors.affiliation: Department of Neurology and Neurosciences, Rutgers NJMS, Newark, NJ, USA. yuan_rui@hotmail.com.
authors.forename: Ruirong
authors.initials: R
authors.lastname: Yuan
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D051959:ELAV Proteins / Q000276:immunology*; D000067779:ELAV-Like Protein 4; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D000922:Immunotoxins / Q000737:chemistry / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009447:Neuroblastoma / Q000188:drug therapy* / Q000276:immunology; D011379:Prognosis; D054789:Ribosome Inactivating Proteins, Type 1 / Q000737:chemistry / Q000494:pharmacology; D000076985:Saporins; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000276:immunology; D019809:Streptavidin / Q000737:chemistry / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D051959:ELAV Proteins; D000067779:ELAV-Like Protein 4; C498011:Elavl4 protein, mouse; D000922:Immunotoxins; D054789:Ribosome Inactivating Proteins, Type 1; D019809:Streptavidin; D000076985:Saporins