Light chain variants of an IgG3 anti-G(D3) monoclonal antibody and the relationship among avidity, effector functions, tumor targeting, and antitumor activity Journal Article
| Authors: | Chapman, P. B.; Lonberg, M.; Houghton, A. N. |
| Article Title: | Light chain variants of an IgG3 anti-G(D3) monoclonal antibody and the relationship among avidity, effector functions, tumor targeting, and antitumor activity |
| Abstract: | R24 is an IgG3 mouse monoclonal antibody which recognizes the ganglioside GD3 Two variants of R24, in which one (V2-R24) or both (V1-R24) light chains were substituted by MOPC-21 light chains, were isolated and characterized. R24 had a 40-fold higher avidity for GD3 than either variant, suggesting that high avidity binding required the presence of two R24 light chains and, thus, divalency. R24 and both variants mediated antibody-dependent cellular cytotoxicity but antibody-dependent cellular cytotoxicity mediated by variants was weak compared to R24. The presence of at least one R24 light chain was required for complement-dependent cytotoxicity; complement-dependent cytotoxicity was mediated by R24 and weakly by V2-R24 but not by V1-R24. R24, but not V1-R24 or V2-R24, inhibited attachment of melanoma cells to plastic and activated T-lymphocytes, suggesting a threshold of avidity required for these biological effects. In a human melanoma xenograft model in nu/nu mice, radiolabeled R24, variants, and isotype-matched control monoclonal antibodies all appeared to localize in tumors (based on tumonnormal tissue ratios), but specific tumor targeting by R24 was generally 3- to 6-fold higher. R24 prevented melanoma outgrowth in nu/nu mice, while V2-R24 induced partial tumor protection. V1-R24 and the negative control monoclonal antibody did not inhibit tumor outgrowth. Antitumor activity of R24 corresponded to avidity and ability to mediate complement-dependent cytotoxicity in vitro. © 1990, American Association for Cancer Research. All rights reserved. |
| Keywords: | human cell; mouse; animal; mice; melanoma; animal experiment; antineoplastic activity; tumor xenograft; tumor cells, cultured; monoclonal antibody; lymphocyte activation; antibodies, monoclonal; immunoglobulin g; genetic engineering; neoplasm transplantation; immunoglobulin light chain; molecular weight; antibody affinity; gangliosides; ganglioside; antibody-dependent cell cytotoxicity; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; immunoglobulins, light-chain |
| Journal Title: | Cancer Research |
| Volume: | 50 |
| Issue: | 5 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 1990-03-01 |
| Start Page: | 1503 |
| End Page: | 1509 |
| Language: | English |
| PUBMED: | 2105840 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 27 January 2020 -- Source: Scopus |
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