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Human fetal brain antigen expression common to tumors of neuroectodermal tissue origin
Authors:C J Wikstrand  M A Bourdon  C N Pegram  D D Bigner
Affiliation:1. Department of Pathology, Duke University Medical Center, Durham, NC 27710, U.S.A.;2. Department of Surgery, Duke University Medical Center, Durham, NC 27710, U.S.A.
Abstract:The antigenic relationship between human tumors of neuroectodermal origin and fetal brain were further investigated by characterization of two hybridoma antibodies derived from a fusion of P3-NS1/1-Ag 4-1 (NSI) myeloma cells and splenocytes hyperimmunized to second trimester human fetal brain homogenate. Monoclonal antibodies (MAs) 1H8cl 2 and 1H8cl 3 were analyzed by cell surface radioimmunoassay (CS-RIA), quantitative absorption, indirect immunofluorescence, and peroxidase-antiperoxidase (PAP) immunohistology. MA 1H8cl 3 is the more broadly reactive, binding to 9/14 glioblastoma (GBM), 2/3 neuroblastoma, 1/2 melanoma, and 1 medulloblastoma cell line(s) by CS-RIA analysis, and to 12/15 GBM, fetal brain, spleen, and liver, and adult spleen by PAP analysis. MA 1H8cl 2 is more restricted, binding to 7/14 GBM, 2/3 neuroblastoma, 1 medulloblastoma, and 2/3 fetal skin fibroblast cell line(s) by CS-RIA, and to 9/15 GBM and fetal brain and spleen by PAP analysis. Control non-central nervous system tumors and normal adult tissue including brain, thymus, lymph node, liver, kidney, lung, skin, and pancreas, were unreactive with both 1H8cl 2 and 1H8cl 3 by CS-RIA, PAP, and absorption analysis. The data presented here establish the unique nature of the detected antigenic specificities as compared to previously described oncofetal and onconeural antigens, and define two immune reagents which are operationally specific for tumors of neuroectodermal origin within the adult central nervous system.
Keywords:BR  binding ratio  CS-RIA  cell surface radioimmunoassay  DPBS  Dulbecco's phosphate-buffered saline  FCS  fetal calf serum  GBM  glioblastoma multiforme  HAT  selection medium (Littlefield 1964)  H  hypoxanthine  A  aminopterin  T  thymidine  HBSS  Hank's balanced salt solution  MA  monoclonal antibody  NSI  myeloma cell line P3-NSI/1-Ag 4-1  PAP  peroxidase-antiperoxidase immunohistochemical assay  ZOG  zinc-option medium, supplemented with gentamicin, glutamine, and 10–20% FCS
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