作者: J Kanellos , IFC McKenzie , GA Pietersz
DOI: 10.1038/ICB.1989.13
关键词: Cancer research 、 Galactose binding 、 Ricin 、 Antibody 、 Monoclonal antibody 、 Immunotoxin 、 Chemistry 、 In vivo 、 Transferrin receptor 、 Spleen
摘要: Immunotoxin conjugates of whole ricin with monoclonal antibody were prepared the galactose binding site on B chain blocked. These ricin-antibody then injected directly into tumours (IT) in mice established solid tumours. The found to be effective, vivo, (C57BL/6XBALB/c)F1 carrying thymoma grafts and nude bearing human tumour xenografts. Thymomas (Ly-1.1-, 2.1+) completely regressed following IT injection either ricin-anti-Ly-2.1 or 'modified' (periodate treated remove carbohydrate) but did not regress when non-reactive ricin-anti-Ly-1.1. Similarly, CEM (transferrin receptor+) HT-29 (17.1/2+) ricin-anti-transferrin receptor ricin-17.1/2 conjugates. disappeared within 48 h, 80-100% these there was no recurrence. Intact require presence lactose block native selective activity entirely dependent reactivity antibodies (MoAb). Further, killing target cells specific because cause regression MoAb alone inhibit growth. In addition, systemic toxicity evident reactive By contrast, only liver spleen due diffusion from tumour; thus moiety immunotoxin serves tumour, hold little escapes. It that conjugate treatment 1-2 micrograms harmful mice, contrast alone, which killed all at a dose 0.5 micrograms. Thus can used successfully vivo for local therapy, leading eradication by direct tumour.