National Institutes of Health, a Component of the US Dept. of Health & Human Services

Naoshi Hagihara

Richard J Youle

Vascular damage has proven to be dose limiting in administering immunotoxins into the brain to treat brain tumors. Vascular toxicity of immunotoxins which rely in part on exposure to lowered pH in cellular endosomes and lysosomes can be avoided by administering an endosome pH-raising agent systemically during some or all of the time that the immunotoxin is present in the brain of the organism. Suitable endosome pH-raising agents include lysosomotrophic amines, proton ionophores, and vacuolar H&plus; ATPase inhibitors. The invention increases the therapeutic window of the immunotoxins and increases the likelihood the treatment will have an effect on the course of the tumor.

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Saga, Japan

Naoshi Hagihara