Compositions and methods for modifying toxic effects of proteinaceous compounds
AssigneeBoard of Regents, The University of Texas System
InventorsEllen S. Vitetta, Victor F. Ghetie, Joan E. Smallshaw, Roxana G. Baluna
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Abstract
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.
Claims67
A modified proteinaceous composition comprising a protein having a (x)D(y) sequence and at least one amino acid mutation that alters the ability of a (x)D(y) sequence to induce Vascular Leak Syndrome.
A modified proteinaceous composition comprising a protein having a (x)D(y) sequence and at least one amino acid mutation in a flanking sequence that alters the toxicity of the protein.
A ricin A chain toxin with a reduced ability to promote toxicity in a patient, wherein at least one amino acid flanking the (x)D(y) sequence altered.
A method of reducing the ability of a proteinaceous composition to reduce induction of VLS, comprising the steps of:
- a) identifying a protein comprising at least one amino acid sequence of (x)D(y), wherein (x) is selected from the group leucine, isoleucine, glycine and valine, and wherein (y) is selected from the group valine, leucine and serine;
- and
- b) altering at least one amino acid residue flanking the (x)D(y) sequence, wherein the ability to induce VLS is reduced.
A method of preparing an immunotoxin with a reduced ability to induce VLS comprising the steps of:
- a) identifying a toxin comprising at least one amino acid sequence of (x)D(y), wherein (x) is selected from the group leucine, isoleucine, glycine and valine, and wherein (y) is selected from the group valine, leucine and serine;
- and
- b) altering at least one amino acid residue flanking the (x)D(y) sequence, wherein the ability to induce VLS is reduced;
- and
- c) conjugating said toxin to a composition comprising at least one antibody to produce an immunotoxin,
- wherein the immunotoxin produced possesses a reduced ability to promote VLS when compared to a like immunotoxin wherein the flanking amino acid sequence was not altered from the toxin.
Dependencies are inferred from the claim text.