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-10814014-B2
Publication Date
2020-10-27
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
The invention provides methods of detecting tumors, monitoring cancer therapy, and selectively inhibiting the proliferation and/or killing of cancer cells by utilizing papilloma pseudoviruses or papilloma virus-like particles (VLPs). These pseudoviruses or VLPs can be labeled with detectable markers such as fluorescent, radioactive, or chemiluminescent labels, which may be chemically coupled or encoded by genes carried within the pseudovirus. Methods include administering the labeled pseudovirus or VLP to a subject and detecting the presence or amount of binding to cancer cells, distinguishing them from normal cells.
The invention addresses significant limitations in current cancer diagnostics and therapies. Existing treatments such as radiation and chemotherapy often cause widespread side effects due to damage to normal tissues, and certain cancers remain untreatable or become resistant to standard therapies. The challenge lies in precisely detecting cancer cells and selectively targeting them without harming normal cells, especially given difficulties posed by inaccessible tumors or metastasis. The papilloma pseudoviruses and VLPs selectively bind to cancer cells but not normal cells, thereby offering a highly specific method for cancer detection, therapeutic monitoring, and targeted treatment.
Claims Coverage
The claims encompass four main inventive features relating to methods of administering papilloma pseudoviruses or VLPs comprising fluorescent dyes, their coupling to surfaces, methods of administration to melanomas, and detection of melanoma cells using these labeled particles.
Use of papilloma pseudoviruses or VLPs containing fluorescent dyes for melanoma detection and treatment
Methods of administering papilloma pseudoviruses or papilloma VLPs comprising a fluorescent dye to a melanoma in a subject, followed by exposure of the fluorescent dye to an excitation wavelength of light to detect or treat the melanoma.
Chemical coupling of fluorescent dyes to papilloma pseudoviruses or VLPs
The fluorescent dye is chemically coupled, specifically to the surface, of the papilloma pseudovirus or papilloma VLP to enable detection and targeting of melanoma cells.
Administration of labeled papilloma pseudoviruses or VLPs into melanomas in the eye
The papilloma pseudoviruses or VLPs comprising fluorescent dyes can be administered by direct injection into melanoma located in the eye of the subject to facilitate specific detection or treatment.
Detection of melanoma cells bound to labeled papilloma pseudoviruses or VLPs
Methods of detecting presence of melanoma cells by administering detectable amounts of papilloma pseudoviruses or VLPs comprising fluorescent dyes to subjects suspected of having melanoma cells and detecting melanoma cells bound to these labeled particles.
The claims focus on the targeted application of papilloma pseudoviruses or VLPs labeled with fluorescent dyes for specific detection and treatment of melanoma, emphasizing chemical coupling of labels, targeted administration particularly in ocular melanoma, and methods for detecting melanoma cells using these labeled viral particles.
Stated Advantages
Papilloma pseudoviruses and VLPs selectively bind to cancer cells but not to normal cells, reducing cytotoxicity to healthy tissues.
Because pseudoviruses preferentially kill cancer cells, they induce selective immune responses against the cancer cells.
The pseudoviruses or VLPs can be rapidly generated for many papillomavirus types, and neutralizing antibody effects can be overcome by switching types to improve therapeutic effectiveness.
The inability to bind normal cells minimizes off-target interactions, enhancing delivery efficiency to cancer cells compared to other viral vectors.
Documented Applications
Detection of tumors, metastases, and pre-malignant conditions by binding of labeled papilloma pseudoviruses or VLPs to cancer cells.
Monitoring efficacy and progression of cancer therapy by administering labeled papilloma pseudoviruses or VLPs and measuring their binding to cancer cells over time.
Selective inhibition of proliferation and killing of cancer cells through administration of papilloma pseudoviruses or VLPs formulated with therapeutic agents such as toxins, radionuclides, or therapeutic genes.
Treatment of various cancers including leukemia, lymphoma, sarcomas, carcinomas, and brain tumors by targeted delivery of therapeutic agents via papilloma pseudoviruses or VLPs.
Use of kits comprising labeled papilloma pseudoviruses or VLPs and pharmaceutical carriers for diagnosis and treatment of cancer, including cervical cancer.
Intraperitoneal administration for ovarian cancer metastases and intravenous administration for lung metastases demonstrated in animal models.
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