Abstract |
Immunotoxins were prepared by linking the type 1 ribosome-inactivating proteins (RIP) momordin I, pokeweed antiviral protein from seeds (PAP-S) and saporin-S6 to the 48-127 monoclonal antibody (MAb) recognising a glycoprotein (gp54) expressed on all human bladder tumours tested and on human bladder carcinoma cell lines, in particular on the T24 cell line. T24 cells required a 2 hr contact with immunotoxins to ensure binding and endocytosis. A time course of exposure, followed by further incubation without the immunotoxins, showed that maximum inhibition of protein synthesis by T24 cells was reached after 2 hr of contact followed by 3 days without the immunotoxins. Under optimal conditions, 48-127/RIP immunotoxins at nanomolar concentrations inhibited by 50% protein synthesis of target T24 cells. No toxicity was observed if (i) target cells were treated with non-conjugated RIP, (ii) target cells were treated with momordin I- or PAP-S-containing immunotoxins made with an irrelevant antibody and (iii) a non-target cell line was treated with the same 2 RIP conjugated to 48-127 antibody. The in vitro selective toxicity of these immunotoxins encourages further studies in view of a possible use in clinical trials for the local therapy of human bladder carcinomas.
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Authors | M G Battelli, L Polito, A Bolognesi, L Lafleur, Y Fradet, F Stirpe |
Journal | International journal of cancer
(Int J Cancer)
Vol. 65
Issue 4
Pg. 485-90
(Feb 08 1996)
ISSN: 0020-7136 [Print] United States |
PMID | 8621232
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Immunotoxins
- Plant Proteins
- Ribosome Inactivating Proteins, Type 1
- Ribosome Inactivating Proteins, Type 2
- momordin I (protein)
- N-Glycosyl Hydrolases
- Saporins
- pokeweed antiviral protein
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Topics |
- Humans
- Immunotoxins
(pharmacology)
- N-Glycosyl Hydrolases
- Plant Proteins
(pharmacology)
- Protein Biosynthesis
- Ribosome Inactivating Proteins, Type 1
- Ribosome Inactivating Proteins, Type 2
- Ribosomes
(drug effects)
- Saporins
- Tumor Cells, Cultured
- Urinary Bladder Neoplasms
(metabolism, pathology, therapy)
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