Papillomavirus pseudoviruses for detection and therapy of tumors
Inventors
Roberts, Jeff • Lowy, Douglas R. • Schiller, John T.
Assignees
National Institutes of Health NIH • US Department of Health and Human Services
Publication Number
US-8394411-B2
Publication Date
2013-03-12
Expiration Date
2028-05-01
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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
Disclosed herein are methods utilizing papilloma pseudoviruses or papilloma virus-like particles (VLPs) for detecting tumors, monitoring cancer therapy, and selectively inhibiting the proliferation or killing of cancer cells. These methods involve administering to a subject a papilloma pseudovirus or VLP that carries a detectable label or therapeutic agent, allowing for specific binding to cancer cells. Detection or therapeutic intervention is then carried out based on the amount or presence of pseudovirus or VLP bound to cancer cells compared to normal cells.
The invention addresses the problem that many cancers remain incurable, untreatable, or resistant to standard therapies, with current treatments causing significant side effects and often lacking specificity. Unlike existing viral vectors that may interact with normal cells leading to toxicity and inefficient targeting, papilloma pseudoviruses and VLPs selectively bind and infect cancer cells, minimizing cytotoxicity to normal tissue and enhancing targeted delivery of therapeutic or diagnostic agents.
Claims Coverage
The patent contains one independent claim encompassing multiple inventive features related to methods of inhibiting cancer cell proliferation or killing cancer cells using therapeutic agents formulated with papilloma pseudoviruses or papilloma VLPs.
Therapeutic agent formulations with papilloma pseudoviruses or VLPs
A method consisting of administering to a subject having cancer a composition comprising a therapeutic agent formulated with a papilloma pseudovirus or a papilloma VLP where the therapeutic agent is selected from tumor suppressor genes, pro-apoptotic genes, cytokine/growth factor/hormone genes, immunomodulatory genes, genes encoding cytotoxic polypeptides, suicide genes, cytotoxins, radionuclides, pro-drugs, and therapeutic nucleic acids.
Chemical coupling of therapeutic agents
The therapeutic agent can be chemically coupled to the papilloma pseudovirus or VLP to achieve targeted delivery to cancer cells.
Incorporation of therapeutic agents within pseudoviruses or VLPs
Alternatively, the therapeutic agent can be incorporated within the papilloma pseudovirus or VLP for selective delivery.
Use of toxins as therapeutic agents
The therapeutic agent can include toxins to selectively inhibit or kill cancer cells.
Use of prodrugs
The therapeutic agent can include prodrugs such as ganciclovir or acyclovir, activated by suicide genes delivered via pseudoviruses or VLPs.
Use of oligo T nucleic acid as therapeutic agent
The therapeutic agent can be oligo T nucleic acid or a nucleic acid expressing oligo T of various lengths (up to 200 nucleotides), operably linked to a Pol III promoter to induce cytotoxicity.
Use of radionuclides as therapeutic agents
The therapeutic agent can be a radionuclide chemically coupled to the pseudovirus or VLP to deliver lethal radiation doses specifically to cancer cells.
The claims collectively cover methods of targeting cancer cells by administering compositions where papilloma pseudoviruses or VLPs deliver a variety of therapeutic agents either chemically coupled or incorporated, with specific examples including genes, toxins, radionuclides, prodrugs, and oligo T nucleic acids, enabling selective inhibition or killing of cancer cells.
Stated Advantages
Papilloma pseudoviruses and VLPs selectively bind and infect cancer cells but not normal cells, minimizing cytotoxicity to normal tissues.
The specificity of pseudoviruses and VLPs toward cancer cells avoids competing interactions with normal cells, enhancing effective delivery of therapeutic agents.
Selective killing of cancer cells via these vectors preferentially induces an immune response against the cancer.
Pseudoviruses and VLPs can be rapidly generated for many papillomavirus types, enabling use of different types to overcome neutralizing antibody inhibition and allow boosting.
Documented Applications
Detecting the presence of cancer cells in subjects by administering detectable papilloma pseudoviruses or VLPs and detecting their specific binding to cancer cells.
Monitoring cancer therapy by measuring the amount of papilloma pseudovirus or VLP bound to cancer cells before, during, and after treatment to assess therapeutic efficacy.
Selective inhibition of cancer cell proliferation and/or killing cancer cells by administering papilloma pseudoviruses or VLPs formulated with therapeutic agents such as genes, toxins, radionuclides, prodrugs, or oligo T nucleic acids.
Diagnostic kits for tumor detection comprising labeled papilloma pseudoviruses or VLPs, pharmaceutical carriers, and instructions for use, including kits for cervical cancer detection.
Treatment of a wide variety of cancers including leukemia, lymphoma, sarcomas, carcinomas of various organs, brain tumors, melanomas, and others by the selective targeting capabilities of papilloma pseudoviruses or VLPs delivering therapeutic agents.
Suicide gene therapy of ovarian carcinoma using HPV pseudoviruses that deliver herpes simplex thymidine kinase followed by prodrug treatment.
Use of oligo T expressing HPV pseudoviruses for combined anti-tumor cytotoxicity and immune activation.
Intravenous administration of HPV pseudoviruses to specifically target lung metastases.
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