Co-expression of tumor antigens and their modulation by pleiotrophic modifiers enhance targeting of human monoclonal antibodies to pancreatic carcinoma.
Cocktails of human monoclonal antibodies (HuMAbs) have been used to increase the likelihood of identifying heterogeneous cancer cells. We utilized 3 HuMAbs termed SK-1, GM4, and GMA1, which recognized a 42-46 kDa two chain structure, a 57 kDa antigen, and the ganglioside GD3, respectively. An estimated two dozen cell lines were tested for the coexpression of these antigens and this was found to be present only on pancreatic carcinoma cell line, PANC-1; A 24 hr treatment of PANC-1 cells with interferon gamma (IFN gamma; 100 units), interferon beta (IFN beta; 1000 units), as well as interferon alpha (IFN alpha; 1000 units) resulted in roughly a four fold increase in the co-expression of the 42-46 kDa/GD3 antigens as well as the 42-46 kDa/57 kDa antigens. After a 4 day incubation the co-expression of these antigens progressed and IFN alpha treatment had the most pronounced effect, which was 8 fold higher than background for the 42-46 kDa/57 kDa antigens, whereas IFN beta resulted in a five fold antigen upregulation. The pronounced effect of vinblastine on the co-expression of the 42-46 kDa/GD3 antigens (4 fold on day 1 and, 10 fold on day 4) and 42-46 kDa/57 kDa antigens on PANC-1 (5 fold on day 1 and 7 fold over background on day 4) cells can be seen at concentrations as low as 10(-7)M. Colchicine and vincristine dramatically enhanced co-expression of these tumor antigens on day 4 but not on day 1 PANC-1 cells. The expression of these antigens was also found to be cell cycle dependent.
Mukerjee
S
S
Novopharm Biotech, Inc., San Diego, CA 92121, USA.
McKnight
M E
ME
Nasoff
M
M
Glassy
M C
MC
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000276:immunology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003078:Colchicine / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D010190:Pancreatic Neoplasms / Q000276:immunology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D014747:Vinblastine / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000972:Antineoplastic Agents, Phytogenic; D016207:Cytokines; D014750:Vincristine; D014747:Vinblastine; D003078:Colchicine