University of Texas System

Victor F Ghetie

Ellen S Vitetta

Roxana G Baluna

Joan Elizabeth Smallshaw

Jonathan W Uhr

The present invention provides methods to produce toxoid vaccines, such as ricin A chain vaccines, with reduced ability to promote vascular leak syndrome (VLS) and catalytic toxicity associated with various proteinaceous toxins, such as ribosome inactivating proteins. The invention also provides toxoids which have been mutated to lack amino acid sequences which induce VLS and toxic catalytic activity.

Ricin A chain mutants lacking enzymatic activity as vaccines to protect against aerosolized ricin

The present invention provides methods to produce immunotoxins (ITs) and cytokines with a reduced ability to promote vascular leak syndrome (VLS). The invention also provides ITs and cytokines which have been mutated to lack amino acid sequences which induce VLS. Also disclosed are methods for producing peptides that inhibit the induction of VLS by ITs and cytokines. Also disclosed are peptides comprising the (x)D(y) sequence to promote the extravasation of other molecules. Toxins mutated in the (x)D(y) motif or active site residues are disclosed for used in vaccines.

Compositions and methods for modifying toxic effects of proteinaceous compounds

The present invention provides methods to produce immunotoxins (ITs) and cytokines with a reduced ability to promote vascular leak syndrome (VLS). The invention also provides ITs and cytokines which have been mutated to lack amino acid sequences which induce VLS.

Immunotoxin preparations are described in which the preparations are enriched for a single species of immunotoxin. Also described are methods for the preparation of the substantially purified immunotoxins (ITs). Also disclosed are methods for determining the most effective species of immunotoxin conjugates for treated diseases and pharmaceutical preparations for such treatments.

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Dallas, TX, United States of America

Victor F Ghetie