Papillomavirus pseudoviruses for detection and therapy of tumors
Inventors
Roberts, Jeff • Lowy, Douglas R. • Schiller, John T.
Assignees
US Department of Health and Human Services
Publication Number
US-8999290-B2
Publication Date
2015-04-07
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 are 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). These methods involve administering a labeled papilloma pseudovirus or VLP to a subject and detecting the presence of cancer cells bound to the labeled pseudovirus or VLP. The label may be chemically coupled to the pseudovirus or encoded by a gene within the pseudovirus, including fluorescent, radioactive, or chemiluminescent labels.
The invention addresses the problem that current cancer therapies have considerable shortcomings, such as causing damage to normal tissues, various side effects, and resistance development. Additionally, tumors may be inoperable or metastatic, making treatment difficult or impossible, highlighting the need for robust diagnostic and therapeutic techniques. Papilloma pseudoviruses and VLPs provide an unexpected advantage by selectively binding to and infecting cancer cells but not normal cells, minimizing cytotoxicity to normal tissues and enabling specific targeting of cancer.
The papilloma pseudoviruses and VLPs can be labeled for detecting cancer cells and monitoring cancer therapy by assessing the level of pseudovirus or VLP bound to cancer cells before, during, or after treatment. Furthermore, the compositions can be formulated with therapeutic agents, such as toxins, radionuclides, or oligo T nucleic acids, to selectively inhibit or kill cancer cells while sparing normal cells. The invention also contemplates kits comprising pseudoviruses or VLPs with labels and pharmaceutical carriers for diagnostic or therapeutic applications.
Claims Coverage
The patent includes three main independent claims covering methods of detecting cancer cells, evaluating cancer therapy, and detecting cervical cancer using papilloma pseudoviruses or VLPs comprising detectable labels.
Method for detecting cancer cells bound to papilloma pseudovirus or VLP
A method comprising identifying a subject with or suspected of cancer; administering a detectable amount of a papilloma pseudovirus or VLP comprising a detectable label; and detecting cancer cells bound to the labeled pseudovirus or VLP.
Method for evaluating cancer therapy by detecting papilloma pseudovirus or VLP binding
A method comprising identifying a subject with cancer; providing a cancer therapy; administering a detectable amount of papilloma pseudovirus or VLP comprising a detectable label; and determining the presence or amount of labeled pseudovirus or VLP bound to cancer cells before, during, or after therapy.
Method for detecting cervical cancer using labeled papilloma VLP
A method comprising providing a subject with a composition of papilloma VLP coupled to a detectable label; removing unbound VLPs; and detecting the presence of cancer cells bound to the labeled VLP.
Together, these claims cover methods for cancer diagnosis and therapy monitoring by utilizing papilloma pseudoviruses or VLPs labeled either chemically or genetically, which specifically bind to cancer cells to enable detection and evaluation of cancer and treatment.
Stated Advantages
Papilloma pseudoviruses and VLPs selectively bind to and infect cancer cells but not normal cells, minimizing cytotoxicity to normal tissues.
They enable specific and efficient delivery of reporter genes or therapeutic agents to cancer cells, improving detection and treatment specificity.
Rapid generation of pseudoviruses or VLPs for many papillomavirus types allows overcoming neutralizing antibodies by switching types.
Preferential infection and killing of cancer cells can induce selective immune responses against tumors.
Documented Applications
Detecting the presence of cancer cells or pre-malignant conditions in subjects by administering labeled papilloma pseudoviruses or VLPs and detecting binding.
Monitoring the efficacy of cancer therapy by repeated administration and detection of pseudovirus or VLP bound to cancer cells during treatment.
Selective inhibition of cancer cell proliferation and killing of cancer cells by administering papilloma pseudoviruses or VLPs coupled or containing therapeutic agents such as toxins, radionuclides, or oligo T nucleic acids.
Use in kits for diagnostic detection of tumors, including cervical cancer, comprising labeled papilloma pseudoviruses or VLPs and instructions for use.
Therapeutic treatment of ovarian cancer via intraperitoneal delivery of therapeutic pseudoviruses and suicide gene therapy.
Intravenous administration of papilloma pseudoviruses targeting lung metastases.
Diagnosis and treatment of cervical cancer using papilloma VLPs coupled to radionuclides administered vaginally.
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