Intratumour therapy of solid tumours with ricin-antibody conjugates.

作者: J Kanellos , IFC McKenzie , GA Pietersz

DOI: 10.1038/ICB.1989.13

关键词: Cancer researchGalactose bindingRicinAntibodyMonoclonal antibodyImmunotoxinChemistryIn vivoTransferrin receptorSpleen

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.

参考文章(24)
Jørgen Fogh, Germain Trempe, New Human Tumor Cell Lines Springer, Boston, MA. pp. 115- 159 ,(1975) , 10.1007/978-1-4757-1647-4_5
J. A. Double, Extracellular Factors Affecting the Response of Tumours to Chemotherapeutic Agents Scientific Basis of Cancer Chemotherapy. pp. 18- 25 ,(1969) , 10.1007/978-3-642-88147-3_2
Philip E. THORPE, Walter C. J. ROSS, Alex N. F. BROWN, Christopher D. MYERS, Alan J. CUMBER, Brian M. J. FOXWELL, J. Tony FORRESTER, Blockade of the galactose-binding sites of ricin by its linkage to antibody. Specific cytotoxic effects of the conjugates. FEBS Journal. ,vol. 140, pp. 63- 71 ,(1984) , 10.1111/J.1432-1033.1984.TB08067.X
John E. Leonard, Ivor Royston, Nathan O. Kaplan, Quing-cheng Wang, Kinetics of Protein Synthesis Inactivation in Human T-Lymphocytes by Selective Monoclonal Antibody-Ricin Conjugates Cancer Research. ,vol. 45, pp. 5263- 5269 ,(1985)
PM Hogarth, Jill Edwards, IF McKenzie, JW Goding, FY Liew, None, Monoclonal antibodies to the murine Ly-2.1 cell surface antigen. Immunology. ,vol. 46, pp. 135- ,(1982)
Bernard J. P. BOURRIE, Pierre CASELLAS, Hildur E. BLYTHMAN, Franz K. JANSEN, Study of the plasma clearance of antibody – ricin‐A‐chain immunotoxins FEBS Journal. ,vol. 155, pp. 1- 10 ,(1986) , 10.1111/J.1432-1033.1986.TB09451.X
Daniel A. Vallera, Walter Runge, Franz K. Jansen, Gilda Weil-Hillman, Cytotoxic effect of anti-Mr 67,000 protein immunotoxins on human tumors in a nude mouse model. Cancer Research. ,vol. 45, pp. 1328- 1336 ,(1985)
FC GREENWOOD, WM HUNTER, JS GLOVER, THE PREPARATION OF 131I-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY Biochemical Journal. ,vol. 89, pp. 114- 123 ,(1963) , 10.1042/BJ0890114
L. Wish, J. Furth, R. H. Storey, Direct determinations of plasma, cell, and organ-blood volumes in normal and hypervolemic mice. Experimental Biology and Medicine. ,vol. 74, pp. 644- 648 ,(1950) , 10.3181/00379727-74-18003