Papillomavirus pseudoviruses for detection and therapy of tumors
Inventors
Roberts, Jeffrey • Lowy, Douglas R. • Schiller, John T.
Assignees
US Department of Health and Human Services
Publication Number
US-10188751-B2
Publication Date
2019-01-29
Expiration Date
2028-05-01
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Disclosed herein are methods of detecting tumors, monitoring cancer therapy, and selectively inhibiting the proliferation and/or killing of cancer cells utilizing a papilloma pseudovirus or a papilloma virus-like particle (VLP).
Core Innovation
This invention relates to methods for detecting tumors, monitoring cancer therapy, and selectively inhibiting the proliferation and/or killing of cancer cells using papilloma pseudoviruses or papilloma virus-like particles (VLPs) which comprise detectable labels or therapeutic agents. The disclosed methods include administering these papilloma pseudoviruses or VLPs to subjects having or suspected of having cancer, detecting cancer cells bound to these entities, and treating the cancer cells with therapeutic agents carried by or coupled to them.
The problem being solved arises from the limitations and side effects of current cancer treatments such as radiation therapy and chemotherapy, which are often toxic, can damage normal tissues, and have limited effectiveness especially when tumors are inoperable or metastasize. There exists a manifest need for robust techniques to diagnose and treat cancer more specifically and effectively with minimal damage to normal cells.
The core innovation disclosed is the unexpected discovery that papilloma pseudoviruses and VLPs selectively bind and infect cancer cells but not normal cells, enabling targeted delivery of detectable labels or therapeutic agents. Such specificity minimizes cytotoxicity to normal tissue and facilitates precise detection and treatment. The invention also provides methods to monitor cancer therapy by measuring papilloma pseudovirus or VLP binding to cancer cells over time. Furthermore, therapeutic genes, toxins, radionuclides, or oligo T nucleic acids can be incorporated or chemically coupled to pseudoviruses or VLPs to selectively inhibit or kill cancer cells.
Claims Coverage
The independent claims define three main inventive features concerning the use of papilloma pseudoviruses or papilloma VLPs with fluorescent dyes for detecting cancer cells, particularly in the eye, and methods of administration and excitation for detection.
Use of papilloma pseudoviruses or VLPs comprising a fluorescent dye for cancer cell detection
Administering to cancer cells in a subject a papilloma pseudovirus or papilloma virus-like particle (VLP) that comprises a fluorescent dye, and exposing the fluorescent dye in cancer cells to an excitation wavelength of light to detect the cancer cells.
Chemical coupling of fluorescent dyes to papilloma pseudoviruses or VLPs
The fluorescent dye is chemically coupled to the pseudovirus or VLP, specifically to the surface, enhancing targeted detection.
Administration of papilloma pseudoviruses or VLPs with fluorescent dyes to cancer cells in the eye
Methods include administering papilloma pseudoviruses or papilloma VLPs chemically coupled to fluorescent dyes specifically to cancer cells in the eye, followed by excitation of the dye to enable detection.
Injection methods for delivery to cancer cells
The papilloma pseudoviruses or VLPs comprising fluorescent dyes can be injected directly into cancer cells or into cancer cells in the eye for improved delivery and detection.
The claims collectively cover methods of selective detection of cancer cells using fluorescently labeled papilloma pseudoviruses or VLPs, chemical coupling of such labels, specific targeting to cancer cells including those in the eye, and the routes of administration primarily by injection.
Stated Advantages
Minimizes cytotoxicity to normal cells by selectively targeting cancer cells.
Enables precise detection of tumors and monitoring of cancer therapy in real time through detectable labels.
Allows for selective delivery of therapeutic agents, including therapeutic genes and radionuclides, to cancer cells enhancing treatment efficacy.
Rapid generation of papilloma pseudoviruses or VLPs with type-restricted neutralizing antibodies overcomes immune limitations through use of multiple types.
The inability of papilloma pseudoviruses and VLPs to attach to normal cells in intact tissues reduces off-target effects and increases safety.
Documented Applications
Methods for detecting presence of tumors and pre-malignant conditions such as dysplasia using papilloma pseudoviruses or VLPs labeled with detectable labels.
Monitoring the efficacy of cancer therapies by repeated administration of labeled papilloma pseudoviruses or VLPs to assess tumor load.
Therapeutic applications including selectively inhibiting proliferation or killing of cancer cells by delivering therapeutic agents such as toxins, radionuclides, therapeutic genes, or oligo T nucleic acids via papilloma pseudoviruses or VLPs.
Treatment of a wide spectrum of cancers including leukemia, lymphoma, various carcinomas, sarcomas, melanomas, and many other solid tumors explicitly listed.
Use in diagnostic and therapeutic kits comprising papilloma pseudoviruses or VLPs with labels and pharmaceutical carriers for detection and treatment of tumors, including cervical cancer.
Application in preclinical animal models for intraperitoneal, intravenous and localized tumor targeting demonstrated for ovarian cancer and lung metastases.
Interested in licensing this patent?