Method of treating a bladder cancer using a chimeric egf-targeted bacterial toxin
AssigneePurdue Research Foundation
InventorsRuben Claudio Aguilar, Timothy L. Ratliff
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Abstract
Provided is a method of treating a bladder cancer in an animal or human comprising: administering to an animal or human patient a therapeutic composition comprising a first fusion protein capable of specifically binding to an epidermal growth factor receptor (EGFR) on the surface of a cancer cell and comprising an epidermal growth factor (EGF) polypeptide conjugated to a bacterial toxin polypeptide and a second fusion protein comprising an anthrax Lethal Factor N-terminus (LFN) conjugated to a Diptheria Toxin A (DTA) catalytic domain.
Claims8
1-10. (canceled)
A therapeutic composition comprising:
- (i) a first fusion protein capable of specifically binding to an EGFR on the surface of a bladder cancer cell, wherein the first fusion protein comprises an epidermal growth factor (EGF) polypeptide conjugated to mutant anthrax Protective Antigen (PA′) polypeptide unable to selectively bind to an anthrax receptor, wherein the mutant anthrax Protective Antigen (PA′) polypeptide comprises the mutations N682A and D683A, or at least one mutation selected from the group consisting of N686A, Y710A, N711A, D712A, P715A, L716A, and I718A, wherein the amino acid positions are numbered as in SEQ ID NO:
- 10;
- (ii) a second fusion protein comprising an anthrax Lethal Factor N-terminus (LFN) conjugated to a Diphtheria Toxin A (DTA) catalytic domain;
- and
- (iii) a pharmaceutically acceptable carrier;
- wherein the therapeutic composition is formulated for delivering an effective amount of the therapeutic composition to the lumen of the bladder of a patient in need thereof for modulating the proliferation or viability of cancer cells in said patient.
A method of delivering a therapeutic agent to a bladder cancer cell in an animal or human patient, said method comprising:
- delivering a dose of a therapeutic composition specifically targeting EGFR-expressing cancer cells to the lumen of the bladder of the patient having an EGFR-expressing bladder cancer tumor on the internal surface of the bladder, wherein the therapeutic composition comprises:
- (i) a first fusion protein capable of specifically binding to an EGFR on the surface of a bladder cancer cell, wherein the first fusion protein comprises an epidermal growth factor (EGF) polypeptide conjugated to mutant anthrax Protective Antigen (PA′) polypeptide unable to selectively bind to an anthrax receptor, wherein the mutant anthrax Protective Antigen (PA′) polypeptide comprises the mutations N682A and D683A, or at least one mutation selected from the group consisting of N686A, Y710A, N711A, D712A, P715A, L716A, and 1718A, wherein the amino acid positions are numbered as in SEQ ID NO:
- 10;
- (ii) a second fusion protein comprising an anthrax Lethal Factor N-terminus (LFN) conjugated to a Diphtheria Toxin A (DTA) catalytic domain;
- and
- (iii) a pharmaceutically acceptable carrier;
A kit comprising a first container having a first fusion protein capable of specifically binding to an epidermal growth factor receptor (EGFR) on the surface of a cancer cell and comprising a first fusion protein comprises an epidermal growth factor (EGF) polypeptide conjugated to mutant anthrax Protective Antigen (PA′) polypeptide unable to selectively bind to an anthrax receptor, wherein the mutant anthrax Protective Antigen (PA′) polypeptide comprises the mutations N682A and D683A, or at least one mutation selected from the group consisting of N686A, Y710A, N711A, D712A, P715A, L716A, and I718A, wherein the amino acid positions are numbered as in SEQ ID NO:
- 10, a second container having a second fusion protein comprising an anthrax Lethal Factor N-terminus (LFN) conjugated to a Diphtheria Toxin A (DTA) catalytic domain, and optionally a third container having a pharmaceutically acceptable carrier, and instructions for preparing a therapeutic composition comprising effective amounts of the first and second fusion proteins and the pharmaceutically acceptable carrier, wherein said therapeutic composition is formulated for delivering an effective amount of the therapeutic composition to the lumen of the bladder of a patient in need thereof for modulating the proliferation or viability of cancer cells in said patient.
Dependencies are inferred from the claim text.