CEACAM6 as a novel target for indirect type 1 immunotoxin-based therapy in pancreatic adenocarcinoma.
Immunotoxins are a potentially powerful approach for targeted anticancer therapy. We evaluated a novel immunotherapeutic strategy targeting the immunoglobulin superfamily member carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6). Using pancreatic adenocarcinoma as a model, we show that crosslinking CEACAM6 induces its cytoplasmic accumulation and that this effect can be utilized to increase the efficacy of antibody-mediated delivery of the ribosomal inhibitory protein saporin. Exposure of cells to anti-CEACAM6 antibody, followed by secondary saporin-conjugated immunoglobulin (IgG), induced marked cytotoxicity, via caspase-mediated apoptosis, in vitro. In an in vivo nude mouse xenograft model, this immunotherapeutic approach markedly suppressed pancreatic adenocarcinoma tumor growth and enhanced tumor apoptosis. Given the prevalence of CEACAM6 overexpression among human malignancies, immunological targeting of this tumor antigen may have therapeutic applicability.
Duxbury
Mark S
MS
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Ito
Hiromichi
H
Ashley
Stanley W
SW
Whang
Edward E
EE
D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D015703:Antigens, CD; D000951:Antigens, Neoplasm / Q000494:pharmacology* / Q000627:therapeutic use; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D058851:GPI-Linked Proteins; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology
D015703:Antigens, CD; D000951:Antigens, Neoplasm; C504117:CEACAM6 protein, human; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases