DNA vaccines against tumor growth and methods of use thereof

Patent metadata

Field	Value
Publication number	US-9655815-B2
Application number	US-201414269998-A
Country	US
Kind code	B2
Filing date	May 5, 2014
Priority date	Mar 24, 2003
Publication date	May 23, 2017
Grant date	May 23, 2017

Abstract

A DNA vaccine suitable for eliciting an immune response against cancer cells comprises a DNA construct operably encoding a cancer-associated Inhibitor of Apoptosis-family protein and an immunoactive gene product, such as a cytokine or a ligand for a natural killer cell surface receptor, in a pharmaceutically acceptable carrier. A preferred cytokine is CCL21. Preferred ligands for a natural killer cell surface receptor include human MICA, human MICB, human ULBP1, human ULBP2, and human ULBP3. The cancer-associated Inhibitor of Apoptosis (IAP)-family protein is preferably a survivin protein or livin protein. Method of inhibiting tumor growth by administering the vaccine of the invention to a mammal is also described.

First claim

We claim:

1. An article of manufacture comprising a DNA vaccine suitable for eliciting an immune response against cancer cells comprising a DNA construct operably encoding at least one survivin protein and at least one CCL 21 cytokine in a pharmaceutically acceptable carrier, wherein the DNA construct is incorporated in an attenuated Salmonella typhimurium vector that targets Peyer's patches in the gut, wherein the DNA vaccine induces a cytotoxic T-lymphocyte immune response against tumor cells when orally administered to the patient, and the attenuated Salmonella typhimurium vector comprises an aroA − , dam − Salmonella typhimurium strain packaged in a hermetically sealed, sterile container, the container having a label affixed thereto, the label bearing printed material identifying the vaccine and providing information useful to an individual administering the vaccine to a patient.

2. A transformed host cell transfected with a plasmid vector comprising a DNA construct operably encoding a survivin protein and a CCL 21 cytokine wherein the DNA construct is incorporated in an attenuated Salmonella typhimurium vector that targets Peyer's patches in the gut, wherein the DNA vaccine induces a cytotoxic T-lymphocyte immune response against tumor cells when orally administered to the patient, and the attenuated Salmonella typhimurium vector comprises an aroA − , dam − Salmonella typhimurium strain.

Assignees

• Scripps Research Inst

Inventors

• Xiang Rong
• Zhou He
• Reisfeld Ralph A

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K2039/523

  expressing foreign proteins · CPC title

• A61J1/05 Primary

  for collecting, storing or administering blood, plasma or medical fluids {(multiple bags systems for separating or storing blood components A61M1/0209); Infusion or perfusion containers} · CPC title

• A61K6/00

  Preparations for dentistry · CPC title

• A61K2039/55522

  Cytokines; Lymphokines; Interferons · CPC title