Complement killing of human neuroblastoma cells: A cytotoxic monoclonal antibody and its F(ab)'(2)-cobra venom factor conjugate are equally cytotoxic Journal Article
| Authors: | Juhl, H.; Petrella, E. C.; Cheung, N. K. V.; Bredehorst, R.; Vogel, C. W. |
| Article Title: | Complement killing of human neuroblastoma cells: A cytotoxic monoclonal antibody and its F(ab)'(2)-cobra venom factor conjugate are equally cytotoxic |
| Abstract: | Only a few monoclonal antibodies mediate complement lysis of tumor cells, but for several antibodies it has been demonstrated that a complement-activating function can be introduced by covalent coupling of cobra venom factor (CVF), a non-toxic glycoprotein which is a structural and functional homologue of human complement component C3. In this study we compared the efficacy of complement killing of human neuroblastoma cells by the complement-activating monoclonal antibody 3F8 directed against the GD2 ganglioside antigen with that of its F(ab')2-CVF conjugate. At equal numbers bound per cell the 3F8 antibody and the 3F8 F(ab')2-CVF conjugate were found to be equally cytotoxic in the presence of complement from several species including human. Maximal killing reached up to 98%. The kinetics of killing and the bivalent metal requirement confirmed that the cytotoxic activity of the 3F8 antibody is mediated via the classical pathway and that of the 3F8 F(ab')2-CVF conjugate via the alternative pathway. To achieve a comparable degree of killing, an approximately eight-fold higher concentration of the 3F8 F(ab')2-CVF conjugate was required which appears to be a consequence of the approximately eight-fold lower binding activity of the 3F8 F(ab')2-CVF conjugate compared to the intact 3F8 antibody. Our data suggest that the coupling of CVF to non-cytotoxic antibodies allows the generation of conjugates with a cytotoxic activity similar to that of inherently cytotoxic antibodies. © 1990. |
| Keywords: | human cell; comparative study; cytotoxicity; tumor cells, cultured; antibodies, monoclonal; cell culture; neuroblastoma; cytotoxicity, immunologic; complement; immunotoxins; complement activation; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; cobrotoxin; immunoglobulins, fab; cobra venoms |
| Journal Title: | Molecular Immunology |
| Volume: | 27 |
| Issue: | 10 |
| ISSN: | 0161-5890 |
| Publisher: | Pergamon-Elsevier Science Ltd |
| Date Published: | 1990-10-01 |
| Start Page: | 957 |
| End Page: | 964 |
| Language: | English |
| DOI: | 10.1016/0161-5890(90)90118-j |
| PUBMED: | 2233757 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 27 January 2020 -- Source: Scopus |
