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Direct inoculation of L<jats:sub>2<\/jats:sub>C lymphoma cells into the cisterna magna of guinea\u2010pigs gives rise to a leptomeningeal pattern of growth, similar to that of human ALL, and to a systemic leukaemia which develops in approximately 14 days. In our model the systemic disease could be controlled with cyclophosphamide while the meningeal disease progressed and provided a target for i.t. immunotoxin. The immunotoxin used consisted of an anti\u2010idiotypic antibody disulphide\u2010bonded to the ribosome\u2010inactivating protein saporin. It was highly cytotoxic to L<jats:sub>2<\/jats:sub>C cells <jats:italic>in vitro<\/jats:italic>, being around 30,000 times more potent than a control immunotoxin at inhibiting protein synthesis. <jats:italic>In vivo<\/jats:italic>, the maximum tolerated dose of i.t. immunotoxin was 10 \u03bcg. From the rate at which radiolabeled immunotoxins appeared in the plasma following i.t. injection, we were able to estimate that its half\u2010life in the cerebrospinal fluid (CSF) was between 1\u00b0 and 2 hr. Intrathecal treatment of guinea\u2010pigs with immunotoxin I day after inoculation of L,C cells into the cisterna magna had a remarkable therapeutic effect. All guinea\u2010pigs treated with 0.5 or 5 \u03bcg of immunotoxin survived, and remained tumour\u2010free for more than 100 days after treatment, while control animals given cyclophosphamide alone or an irrelevant immunotoxin had a mean survival time of 28 days. Provided concerns over toxicity can be overcome, these results indicate that i.t. immunotoxins offer an alternative, highly specific form of treatment in leptomeningeal neoplasia.<\/jats:p>","DOI":"10.1002\/ijc.2910470621","type":"journal-article","created":{"date-parts":[[2007,2,19]],"date-time":"2007-02-19T22:03:27Z","timestamp":1171922607000},"page":"909-915","source":"Crossref","is-referenced-by-count":14,"title":["Intra\u2010thecal treatment of leptomeningeal lymphoma with immunotoxin"],"prefix":"10.1002","volume":"47","author":[{"given":"Catherine E.","family":"Urch","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew J. 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