Human antibody SC-1 reduces disseminated tumor cells in nude mice with human gastric cancer

Oncol Rep. 2005 Apr;13(4):765-70.

Abstract

Advanced gastric cancer is a systemic disease that requires adjuvant therapy targeted at eliminating disseminated tumor cells (DTCs). We investigated whether the apoptosis-inducing human monoclonal IgM antibody SC-1 was able to reduce the number of disseminated gastric cancer cells in blood and bone marrow. Human gastric tumor specimens with positive expression of the SC-1 receptor were transplanted in nude mice with metastasizing gastric cancer. After tumor growth (4-6 weeks) animals were randomly allocated to intraperitoneal 100 microg SC-1 (n=23) or 100 microg human IgM (n=23). One week later, animals were sacrificed and blood and bone marrow specimens were obtained. A nested RT-PCR for cytokeratin 20 (CK-20) from blood and bone marrow of mice was performed for detection of disseminated tumor cells. Animals receiving SC-1 had significantly fewer DTCs than did control animals (p=0.0011). None of the SC-1 mice had DTCs simultaneously in both blood and bone marrow versus four of the control animals (p=0.0363). The reduction of DTCs in SC-1 animals was due to reduction in bone marrow (p=0.032 compared to controls), but not in blood (p=0.1158). Treatment with SC-1 significantly reduced the number of DTCs in bone marrow in this animal model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Humanized
  • Bone Marrow Cells / metabolism
  • CD55 Antigens / biosynthesis
  • Cell Line, Tumor
  • DNA, Complementary / metabolism
  • Disease Models, Animal
  • Female
  • Humans
  • Immunoglobulin M / chemistry
  • Immunotherapy / methods*
  • Intermediate Filament Proteins / blood
  • Intermediate Filament Proteins / metabolism
  • Keratin-20
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms / therapy*
  • Time Factors

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • CD55 Antigens
  • DNA, Complementary
  • Immunoglobulin M
  • Intermediate Filament Proteins
  • KRT20 protein, human
  • Keratin-20
  • SC-1 monoclonal antibody