Virus-like particle conjugates for diagnosis and treatment of tumors
Inventors
de los Pinos, Elisabet • Schiller, John Todd • Kines, Rhonda C. • MacDougall, John
Assignees
Aura Biosciences Inc • US Department of Health and Human Services
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Publication Number
US-11806406-B2
Publication Date
2023-11-07
Expiration Date
2034-09-18
Abstract
The present disclosure is directed to methods and compositions for the diagnosis and/or treatment of tumors, such as ocular tumors, using virus-like particles conjugated to photosensitive molecules.
Core Innovation
The invention relates to methods and compositions for the diagnosis and treatment of tumors, particularly ocular tumors, using virus-like particles (VLPs) conjugated to photosensitive molecules. These VLPs, assembled from papilloma virus capsid proteins including L1 and L2 proteins, are modified to carry multiple photosensitive molecules capable of being photoactivated by light. Upon light activation, these molecules induce toxicity selectively in tumor cells without harming healthy cells.
The invention addresses the challenge in photodynamic therapy of delivering high concentrations of photosensitive molecules exclusively to tumor cells. The disclosed photosensitive VLPs overcome limitations of antibody-based delivery systems, which have restricted capacity for photosensitive molecules and limited efficacy where tumor-specific surface markers are not identified. Unexpectedly, conjugation of photosensitive molecules to VLPs does not impair their tumor-targeting binding properties, including binding to heparan sulphate proteoglycans on tumor cells, preserving specificity and enabling effective tumor localization.
The VLPs display enhanced delivery capacity, with examples ranging from about 10 to 1000 photosensitive molecules conjugated per particle, and multiple photosensitive molecules per capsid protein. The photosensitive molecules include infrared dyes such as IR700, porphyrins, and chlorophyll derivatives activated by wavelengths of light suitable for therapeutic or diagnostic purposes. Methods comprise administering these photosensitive VLPs to subjects with tumors, followed by controlled light activation to visualize or selectively kill tumor cells, applicable to various tumor types including ocular melanoma.
Claims Coverage
The patent contains 17 independent claims covering methods of treating ocular tumors with photosensitive VLPs and compositions of viral-like nanoparticles with photosensitizer conjugation.
Method of treating ocular tumors with photosensitive viral-like nanoparticles
Administering viral-like nanoparticles comprising human papilloma virus capsid proteins conjugated to photosensitizer molecules to an ocular tumor and exposing the nanoparticles to activating light to induce cytotoxicity.
Administration route specificity with suprachoroidal injection
Injecting the viral-like nanoparticles into the suprachoroidal space of the eye for targeted treatment of ocular tumors.
Activation timing of photosensitizer molecules
Exposing the viral-like nanoparticles to infrared laser light about 30 minutes to 48 hours after administration to achieve cytotoxic activation.
Composition of viral-like nanoparticles with specific HPV capsid proteins
The viral-like nanoparticles comprise human papilloma virus L1 capsid proteins, including variant HPV16/31 L1 proteins, optionally combined with HPV L2 capsid proteins, conjugated to photosensitizer molecules.
Use of infrared dye molecules as photosensitizers and specific wavelengths for activation
Photosensitizer molecules are infrared dyes such as IR700, activated by light wavelengths in the range of 600 nm to 800 nm, specifically 680 nm to 800 nm.
Method of treating ocular tumors with viral-like particles conjugated to IR700 dye molecules
Administering viral-like nanoparticles comprising HPV L1 capsid proteins conjugated to IR700 dye molecules and activating with 680 to 800 nm light.
Viral-like nanoparticle compositions with human papilloma virus capsid proteins conjugated to photosensitizer molecules
Viral-like nanoparticles including HPV L1 capsid proteins, optionally variant HPV16/31 L1 and HPV L2 capsid proteins, conjugated to IR700 dye molecules.
The claims cover methods for administering and activating photosensitive viral-like nanoparticles comprising HPV capsid proteins conjugated to photosensitizers for diagnosis and treatment of ocular tumors, as well as compositions of such viral-like nanoparticles with defined capsid proteins and photosensitizer conjugation.
Stated Advantages
Photosensitive VLPs offer high-capacity delivery of photosensitive molecules compared to antibodies, enabling delivery of up to 1000 molecules per particle.
VLP conjugation does not interfere with tumor targeting or binding to tumor cell surface heparan sulphate proteoglycans, maintaining specificity and minimizing off-target effects.
The ability to selectively kill tumor cells upon controlled light activation while sparing healthy cells.
Applicability to tumors lacking known tumor-specific surface markers, such as ocular melanoma, expanding treatment options where antibody targeting is ineffective.
Potential use as diagnostic imaging agents due to fluorescent or infrared light activation.
Photosensitive VLPs can treat distant metastases and pre-cancerous lesions effectively.
Documented Applications
Diagnosis and treatment of ocular tumors, including ocular melanoma and metastatic tumors in the eye.
Treatment of various tumors located in the lung, pleura, liver, pancreas, stomach, esophagus, colon, breast, ovary, prostate, brain, meninges, testis, gastrointestinal tract, kidneys, bladder, head, neck, cervix, larynx, or skin.
Photodynamic therapy employing photosensitive VLPs conjugated to infrared dyes activated by specific wavelengths of light.
Selective killing of cancerous tumor cells without harming non-cancerous cells through light-activated toxicity.
Use in tumor imaging and diagnosis by administering photosensitive viral-like particles and detecting fluorescence upon light activation.
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