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Toxicity of ribosome‐inactivating proteins‐containing immunotoxins to a human bladder carcinoma cell line
Author(s) -
Battelli Maria Giulia,
Polito Letizia,
Bolognesi Andrea,
Lafleur Louis,
Fradet Yves,
Stirpe Fiorenzo
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960208)65:4<485::aid-ijc16>3.0.co;2-9
Subject(s) - immunotoxin , ribosome inactivating protein , toxicity , cancer research , carcinoma , cell culture , translation (biology) , ribosome , medicine , biology , pathology , oncology , immunology , antibody , biochemistry , monoclonal antibody , rna , gene , genetics , messenger rna
Immunotoxins were prepared by linking the type I 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. © 1996 Wiley‐Liss, Inc.