caa a22 4500 469073586 CHVBK 20180323132928.0 cr unu---uuuuu 170328e19921101xx s 000 0 eng 10.1007/BF01789015 doi (NATIONALLICENCE)springer-10.1007/BF01789015 Antitumour activity of a sterically blocked ricin immunotoxin on a human colorectal adenocarcinoma grafted subcutaneously in nude mice [Elektronische Daten] [Paola Brusa, Franco Dosio, Francesca Pietribiasi, Laura Delprino, Paola Feraiorni, Massimo Mariani, Giovanni Bussolati, Luigi Cattel] Summary: We prepared a ricin-antibody conjugate, lacking the ability to bind the galactosidic residues of Sepharose 6B, a so-called blocked immunotoxin. The monoclonal antibody AR-3 was cross-linked to ricin through a thioether bond. Further studies showed that the immunoconjugate suppressed the tumour growth of HT-29 cells in intraperitoneally grafted nude mice, without showing any undesirable ricin toxicity. In this work, to demonstrate the therapeutic activity of the AR-3—ricin conjugate injected into mice bearing subcutaneous tumour, we first evaluated its pharmacokinetic behaviour and biodistribution. The behaviour of the immunoconjugate injected intravenously was almost intermediate between that of the antibody and ricin. Moreover, when the immunotoxin was intravenously administered to nude mice bearing subcutaneous tumour, no therapeutic effects appeared, in accordance with the relatively low permeability of the immunotoxin from the blood to the skin. In contrast, peritumoral treatment produced a strong reduction of the neoplastic nodules without substantial regrowth of the malignant cells. This result was also achieved when the immunotoxin treatment was performed on a well-established tumour. This finding was strictly related to the specificity of the immunoconjugate, since the analogous treatment with an irrelevant immunotoxin showed therapeutic failure. Springer-Verlag, 1992 Drug targeting nationallicence Immunotoxin nationallicence Pharmacokinetics nationallicence Antitumoral therapy nationallicence Brusa Paola Istituto di Chimica Farmaceutica Applicata, C.so Raffaello, 31, I-10 125, Torino, Italy aut Dosio Franco Istituto di Chimica Farmaceutica Applicata, C.so Raffaello, 31, I-10 125, Torino, Italy aut Pietribiasi Francesca Dipartimento di Scienze Biomediche e Oncologia Umana, Torino, Italy aut Delprino Laura Istituto di Chimica Farmaceutica Applicata, C.so Raffaello, 31, I-10 125, Torino, Italy aut Feraiorni Paola Istituto di Microbiologia, Torino, Italy aut Mariani Massimo Sorin Biomedica, Saluggia, Italy aut Bussolati Giovanni Dipartimento di Scienze Biomediche e Oncologia Umana, Torino, Italy aut Cattel Luigi Istituto di Chimica Farmaceutica Applicata, C.so Raffaello, 31, I-10 125, Torino, Italy aut Cancer Immunology, Immunotherapy Springer-Verlag 35/6(1992-11-01), 373-380 0340-7004 35:6<373 1992 35 262 https://doi.org/10.1007/BF01789015 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF01789015 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Brusa Paola Istituto di Chimica Farmaceutica Applicata, C.so Raffaello, 31, I-10 125, Torino, Italy aut NATIONALLICENCE 700 1- Dosio Franco Istituto di Chimica Farmaceutica Applicata, C.so Raffaello, 31, I-10 125, Torino, Italy aut NATIONALLICENCE 700 1- Pietribiasi Francesca Dipartimento di Scienze Biomediche e Oncologia Umana, Torino, Italy aut NATIONALLICENCE 700 1- Delprino Laura Istituto di Chimica Farmaceutica Applicata, C.so Raffaello, 31, I-10 125, Torino, Italy aut NATIONALLICENCE 700 1- Feraiorni Paola Istituto di Microbiologia, Torino, Italy aut NATIONALLICENCE 700 1- Mariani Massimo Sorin Biomedica, Saluggia, Italy aut NATIONALLICENCE 700 1- Bussolati Giovanni Dipartimento di Scienze Biomediche e Oncologia Umana, Torino, Italy aut NATIONALLICENCE 700 1- Cattel Luigi Istituto di Chimica Farmaceutica Applicata, C.so Raffaello, 31, I-10 125, Torino, Italy aut NATIONALLICENCE 773 0- Cancer Immunology, Immunotherapy Springer-Verlag 35/6(1992-11-01), 373-380 0340-7004 35:6<373 1992 35 262 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer