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.

Battelli M.G., Polito L., Bolognesi A., Lafleur L., Fradet Y., Stirpe F. (1996). Toxicity of ribosome-inactivating proteins-containing immunotoxins to a human bladder carcinoma cell line. INTERNATIONAL JOURNAL OF CANCER, 65(4), 485-490 [10.1002/(SICI)1097-0215(19960208)65:4<485::AID-IJC16>3.0.CO;2-9].

Toxicity of ribosome-inactivating proteins-containing immunotoxins to a human bladder carcinoma cell line

Battelli M. G.;Polito L.;Bolognesi A.;Stirpe F.
1996

Abstract

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
Battelli M.G., Polito L., Bolognesi A., Lafleur L., Fradet Y., Stirpe F. (1996). Toxicity of ribosome-inactivating proteins-containing immunotoxins to a human bladder carcinoma cell line. INTERNATIONAL JOURNAL OF CANCER, 65(4), 485-490 [10.1002/(SICI)1097-0215(19960208)65:4<485::AID-IJC16>3.0.CO;2-9].
Battelli M.G.; Polito L.; Bolognesi A.; Lafleur L.; Fradet Y.; Stirpe F.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/959187
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