Clinically effective monoclonal antibody 3F8 mediates nonoxidative lysis of human neuroectodermal tumor cells by polymorphonuclear leukocytes Journal Article
| Authors: | Kushner, B. H.; Cheung, N. K. V. |
| Article Title: | Clinically effective monoclonal antibody 3F8 mediates nonoxidative lysis of human neuroectodermal tumor cells by polymorphonuclear leukocytes |
| Abstract: | Most studies of antibody-dependent cellular cytotoxicity (ADCC) by polymorphonuclear leukocytes (PMN) have supported oxidative lytic processes. This may be because the studies used nonhuman or nonneoplastic cells that were highly sensitive to reactive oxygen species or were small enough to be phagocytosed by PMN. We therefore investigated whether oxygen radicals participate in PMN cytotoxicity toward human neuroectodermal solid tumor cells sensitized by 3F8, which is an antiganglioside GDI murine IgG3 monoclonal antibody with documented anticancer activity in humans. A 4-h !'Cr release assay was used to assess tumor cell lysis by hydrogen peroxide, Superoxide, and hypochlorite. Nine of 11 (i]iz(+) human melanoma and neuroblastoma cell lines had equal or greater resistance to these oxidants as compared to a (n<;(-) human carcinoma line (SKBrl-III) found by others (and confirmed by us) to be significantly more resistant to oxidative lysis than a murine cell line (P388D|) representative of those commonly used in cytotoxicity assays. To facilitate detection of oxidant-mediated lysis, subsequent studies of 3F8-mediated ADCC used <‎.(+)targets that were relatively sensitive and others that were relatively resistant to oxygen radicals. Normal PMN and PMN obtained from children with chronic granulomatous disease, which do not generate reactive oxygen species, were equally effective in ADCC. Granulocyte-macrophage colony-stimulating factor, which primes oxidative responses of normal but not of chronic granulomatous disease PMN, enhanced ADCC by both kinds of PMN. During ADCC of 3F8-sensitized targets, with or without granulocytemacrophage colony-stimulating factor, <n<j(-) “innocent bystander” tu mor cells (including P388Dt) were not lysed, a finding consistent with unimportant extracellular release of cytotoxic mediators. Finally, antioxidant and antimyeloperoxidase moieties did not block ADCC. We con clude that oxidants are not key factors in 3F8-mediated lysis by PMN of human neuroectodermal tumor cells. © 1991, American Association for Cancer Research. All rights reserved. |
| Keywords: | neoplasm; metabolism; cell survival; melanoma; oxygen; pathology; tumor cells, cultured; monoclonal antibody; immunology; antibodies, monoclonal; neutrophil; immunotherapy; cell culture; neuroblastoma; neutrophils; neoplasms, germ cell and embryonal; antibody dependent cellular cytotoxicity; gangliosides; ganglioside; free radicals; free radical; antibody-dependent cell cytotoxicity; human; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s. |
| Journal Title: | Cancer Research |
| Volume: | 51 |
| Issue: | 18 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 1991-09-15 |
| Start Page: | 4865 |
| End Page: | 4870 |
| Language: | English |
| PUBMED: | 1654202 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 27 September 2019 -- Source: Scopus |
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