Supra-additive cytotoxic effects of a combination of cytostatic drugs and antibody-induced complement activation on tumor cells in vitro.
Chemotherapy with cytostatic and cytotoxic drugs is the main treatment modality for disseminated cancer. However, despite initial clinical responses seen in certain histotypes, such as small cell lung cancer, relapses mostly occur with chemoresistant phenotypes. In order to prolong the relapse-free period, a combination of chemo- and immunotherapy might offer a new treatment strategy. Here, we have tested our hypothesis that complement activation, induced by monoclonal antibodies, in combination with cytostatic drugs may result in additive cytotoxicity in vitro. Doxorubicin, cisplatinum and etoposide were tested in combination with human complement and a murine monoclonal antibody (MAb F12) directed against the tumor-associated ganglioside antigen fucosyl GM1 on a rat hepatoma (H4-II-E) cell line which was used as tumor model. Using the MTT assay to measure cell survival, supra-additive (i.e. synergistic) cytotoxic effects were seen with each of the cytostatic drugs, the strongest being observed with doxorubicin. These results show promise for further research exploring possible prognostically favorable interactions between cytostatic drugs and monoclonal antibodies in the treatment of cancer.
Brezicka
T
T
Department of Respiratory Medicine and Allergology, University of Göteborg, Sweden. thomas.brezicka@hjl.gu.se
Einbeigi
Z
Z
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004396:Coloring Agents / Q000494:pharmacology; D003131:Combined Modality Therapy; D003167:Complement Activation / Q000187:drug effects*; D003165:Complement System Proteins / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D005677:G(M1) Ganglioside / Q000276:immunology; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy; D051379:Mice; D010641:Phenotype; D051381:Rats; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D004396:Coloring Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D005677:G(M1) Ganglioside; D005047:Etoposide; D004317:Doxorubicin; D003165:Complement System Proteins; C022616:thiazolyl blue; D002945:Cisplatin