Human antibody SC-1 reduces disseminated tumor cells in nude mice with human gastric cancer.
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.
Illert
Bertram
B
Department of Surgery, Chirurgische Klinik I, Center of Operative Medicine, University of Würzburg, Oberdürrbacher Str. 6, D-97080 Würzburg, Germany. illert_b@chirurgie.uni-wuerzburg.de
Otto
Christoph
C
Vollmers
H Peter
HP
Hensel
Frank
F
Thiede
Arnulf
A
Timmermann
Wolfgang
W
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D001854:Bone Marrow Cells / Q000378:metabolism; D018958:CD55 Antigens / Q000096:biosynthesis; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000737:chemistry; D007167:Immunotherapy / Q000379:methods*; D007381:Intermediate Filament Proteins / Q000097:blood / Q000378:metabolism; D053554:Keratin-20; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016133:Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000628:therapy*; D013997:Time Factors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018958:CD55 Antigens; D018076:DNA, Complementary; D007075:Immunoglobulin M; D007381:Intermediate Filament Proteins; C507499:KRT20 protein, human; D053554:Keratin-20; C111124:SC-1 monoclonal antibody