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 • AB Biosciences Inc • US Department of Health and Human Services
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Publication Number
US-12029794-B2
Publication Date
2024-07-09
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 provides methods and compositions for the diagnosis and/or treatment of tumors, such as ocular tumors, using virus-like particles (VLPs) conjugated to photosensitive molecules. These photosensitive viral-like nanoparticles can be selectively delivered to tumor cells and activated by light exposure to produce cytotoxic effects, enabling selective killing of cancerous cells without harming healthy cells.
The problem addressed by the invention is the difficulty in treating certain cancers, particularly ocular cancers like ocular melanoma, which have limited effective treatment options and often result in undesirable side effects. Existing therapies such as surgery and radiation are invasive and can cause complications including cataract formation, radiation-induced retinopathy, and necrosis, highlighting the need for novel therapies that are both targeted and less harmful.
The disclosure reveals that virus-like particles comprising L1 capsid proteins, or combinations of L1 and L2 capsid proteins, can be conjugated with a large number of photosensitive molecules (ranging from about 50 to 1000 or more per particle) without compromising their tumor-targeting ability. The photosensitive molecules, including fluorescent dyes, infrared dyes, porphyrin molecules, and others, can be covalently conjugated to capsid proteins, typically through amide bonds to amino acids such as lysine residues. Upon light activation (infrared, near-infrared, or ultraviolet), these photosensitive molecules induce cytotoxicity specifically in tumor cells due to the targeted delivery by VLPs.
Claims Coverage
The patent contains 3 independent claims focusing on methods of administering virus-like particles conjugated to photosensitizer molecules and activating their cytotoxicity by light exposure.
Methods for administering VLPs conjugated with photosensitizer molecules and activating cytotoxicity by light
Methods comprising administering to a subject virus-like particles comprising viral capsid proteins conjugated with about 50 to 1000 photosensitizer molecules and applying infrared, near-infrared, or ultraviolet light that activates cytotoxicity of the photosensitizer molecules on cancerous cells.
Injection of VLPs into tumors followed by light activation
Methods involving injecting virus-like particles comprising viral capsid proteins conjugated with about 100 to 500 photosensitizer molecules directly into tumors, followed by applying light of specified wavelengths (such as about 700 nm or 800 nm) to activate cytotoxicity of the photosensitizers.
Administration and light exposure for activating cytotoxicity using conjugated VLPs
Methods involving administering virus-like particles conjugated with about 100 to 500 photosensitizer molecules and exposing them to infrared or near-infrared light (e.g., around 700 nm or 800 nm) to activate the cytotoxic effect of the photosensitizer molecules in subjects having cancerous cells or tumors.
The claims focus on methods of using virus-like particles conjugated to photosensitizer molecules in specified amounts, particularly about 50 to 1000 per particle, to target cancerous cells. Light sources including infrared, near-infrared, or ultraviolet light are applied to activate cytotoxicity, and various administration routes (intravenous or direct tumor injection) and tumor types are encompassed.
Stated Advantages
Photosensitive viral-like nanoparticles can carry a much higher payload of photosensitive molecules compared to antibodies, enabling enhanced targeting and cytotoxicity toward tumor cells.
Conjugation of photosensitive molecules does not interfere with VLP tumor targeting or binding to tumor cell surface components like heparan sulphate proteoglycans.
The photosensitive virus-like particles facilitate selective killing of tumor cells with minimal damage to healthy cells, offering a potentially safer and more effective cancer treatment.
The VLP-based system can target tumors that lack identified tumor-specific receptors and are not amenable to antibody-based targeting, expanding the range of treatable tumors.
The use of photosensitive molecules enables dual functions including tumor imaging and therapy, through activation at different wavelengths to visualize or kill tumor cells.
Documented Applications
Diagnosis and treatment of ocular tumors, including ocular melanoma and tumors metastasized to the eye.
Treatment of tumors located in various organs and tissues such as lung, pleura, liver, pancreas, stomach, esophagus, colon, breast, ovary, prostate, brain, meninges, testis, kidney, bladder, head, neck, cervix, larynx, and skin.
Selective inhibition or killing of cancerous cells while sparing non-cancerous cells using VLP conjugates activated by light.
Treatment and diagnosis of metastatic tumors and pre-cancerous lesions (e.g., ocular nevi).
Use of photosensitive viral-like particles for photodynamic therapy (light-activated therapy) and tumor imaging in vivo.
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