US20150343060A1 - Treatment of circulating tumor cells using an extracorporeal device - Google Patents

Treatment of circulating tumor cells using an extracorporeal device Download PDF

Info

Publication number
US20150343060A1
US20150343060A1 US14/728,204 US201514728204A US2015343060A1 US 20150343060 A1 US20150343060 A1 US 20150343060A1 US 201514728204 A US201514728204 A US 201514728204A US 2015343060 A1 US2015343060 A1 US 2015343060A1
Authority
US
United States
Prior art keywords
subject
blood
ctcs
ctc
cells
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US14/728,204
Other languages
English (en)
Inventor
Joy L. Kovar
Han-Wei Wang
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Rakuten Medical Inc
Original Assignee
Li Cor Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Li Cor Inc filed Critical Li Cor Inc
Priority to US14/728,204 priority Critical patent/US20150343060A1/en
Assigned to LI-COR, INC. reassignment LI-COR, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: KOVAR, JOY L., WANG, HAN-WEI
Publication of US20150343060A1 publication Critical patent/US20150343060A1/en
Assigned to Rakuten Medical, Inc. reassignment Rakuten Medical, Inc. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: LI-COR, INC.
Abandoned legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
    • A61K41/0071—PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/10—Inactivation or decontamination of a medicinal preparation prior to administration to an animal or a person
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/6415—Toxins or lectins, e.g. clostridial toxins or Pseudomonas exotoxins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/642—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent the peptide or protein in the drug conjugate being a cytokine, e.g. IL2, chemokine, growth factors or interferons being the inactive part of the conjugate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6849—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/0013—Luminescence
    • A61K49/0017—Fluorescence in vivo
    • A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
    • A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
    • A61K49/0032—Methine dyes, e.g. cyanine dyes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/0013—Luminescence
    • A61K49/0017—Fluorescence in vivo
    • A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/041—Heterocyclic compounds
    • A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
    • A61K51/0446—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/0497—Organic compounds conjugates with a carrier being an organic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • A61K51/082—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins the peptide being a RGD-containing peptide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • A61K51/083—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins the peptide being octreotide or a somatostatin-receptor-binding peptide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • A61K51/088—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins conjugates with carriers being peptides, polyamino acids or proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3618—Magnetic separation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3621—Extra-corporeal blood circuits
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3681—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits by irradiation
    • A61M1/3683—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits by irradiation using photoactive agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3681—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits by irradiation
    • A61M1/3683—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits by irradiation using photoactive agents
    • A61M1/3686—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits by irradiation using photoactive agents by removing photoactive agents after irradiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0613—Apparatus adapted for a specific treatment
    • A61N5/062—Photodynamic therapy, i.e. excitation of an agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/10—Anti-acne agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/0013—Luminescence
    • A61K49/0017—Fluorescence in vivo
    • A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
    • A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
    • A61K49/0036—Porphyrins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/0658—Radiation therapy using light characterised by the wavelength of light used

Definitions

  • Tumor metastasis is the process in which cancer cells spread from the site of a primary solid tumor to one or more other organs in the body.
  • the cancer cells such as circulating tumor cells (CTCs)
  • CTCs circulating tumor cells
  • Solid tumors are treated by therapies including surgery, radiotherapy, chemotherapy and targeted antibody therapy.
  • Photoimmunotherapy using photosensitizing moiety or biomolecule-fluorophore conjugates has been described as a possible treatment as well (see, e.g., U.S. Pat. No. 8,524,239).
  • Photosensitizing antibody-fluorophore conjugates can utilize phthalocyanine dyes, such as IRDye® 700DX (LI-COR Biosciences, Lincoln, Nebr.) which has low sensitivity to photobleaching and is highly photostable (see, e.g., U.S. Pat. No. 7,005,518).
  • phthalocyanine dyes such as IRDye® 700DX (LI-COR Biosciences, Lincoln, Nebr.) which has low sensitivity to photobleaching and is highly photostable (see, e.g., U.S. Pat. No. 7,005,518).
  • These dyes can be conjugated to various biomolecules, such as antibodies or fragments thereof, antibodies, nanobodies, Affibodies®, diabodies, minibodies, antigens, ligands, proteins, peptides, carbohydrates, nucleic acids, small molecules, pseudovirion, etc.
  • the phthalocyanine dye When exposed to excitation light, the phthalocyanine dye generates a cytotoxic singlet oxygen that can induce cell death, such as through apoptosis, necrosis or autophagy. Two types of reactions occur, Type I generates radicals and Type II generates singlet oxygen. Both radicals and singlet oxygen cause oxidative destruction of tissues. It has been shown that the administration of photodynamic therapy using IRDye® 700DX-anti-HER2 + antibodies can decrease the size of HER2 + solid tumors in a mouse model (Mitsunaga et al., Nat. Med., 2011, 17(12):1685-1691).
  • Photodynamic therapy with photosensitizer can be performed with different forms of light sources (see, e.g., U.S. Pat. Nos. 5,976,175 and 8,175,687) to enable excitation light reaching different body locations.
  • Whole body exposure with tanning bed (U.S. Pat. No. 6,896,693) or long-term treatment with wearable devices (U.S. Pat. No. 7,850,720) has been demonstrated.
  • One of key factors in these kinds of methods is the extensive extinction of excitation light when passing through skins, soft tissues, or organs.
  • Extracorporeal blood treatment eliminates the concern of light absorption through thick tissue layers.
  • extracorporeal devices have been applied to patients for different treatment such as hemodialysis, extracorporeal oxygenation, CO 2 removal, and apheresis, etc.
  • the knowledge on extracorporeal circulation is thus well established and broadly applied.
  • photopheresis utilizes separation of blood compositions and applies UV light to the concentrated part (e.g. white blood cells) before returning the recombined blood components to the patient.
  • the photopheresis or extracorporeal photochemotherapy see, e.g., U.S. Patent Publication Nos.
  • the number of CTCs in a patient can be estimated via the CELLSEARCH® System (Janssen Diagnostics, LLC, Raritan, N.J.).
  • the system utilizes ferrofluid nanoparticles with epithelial cell adhesion targeting antibodies to enumerate CTCs from the bulk of 7.5 ml blood samples.
  • the CTCs are then distinguished with immunofluoresence dyes under a microscopic imaging system for diagnosis purpose.
  • the system renders the monitoring of metastatic cancer patients throughout treatment to making informed clinical decisions.
  • a method for inducing apoptosis, necrosis or autophagy resulting in cell death of circulating tumor cells (CTCs) in a subject comprises (a) administering to the subject's blood a therapeutically effective agent comprising a near-infrared phthalocyanine dye conjugated to an moiety or biomolecule that specifically binds to CTCs; (b) ex vivo irradiating the subject's blood with an appropriate excitation light in an amount to effectively induce apoptosis, necrosis and/or autophagy in the CTCs; and (c) re-introducing the treated blood into the subject.
  • a therapeutically effective agent comprising a near-infrared phthalocyanine dye conjugated to an moiety or biomolecule that specifically binds to CTCs
  • ex vivo irradiating the subject's blood with an appropriate excitation light in an amount to effectively induce apoptosis, necrosis and/or autophagy in the CTCs
  • the subject has a solid tumor or has had a solid tumor.
  • the solid tumor is a breast tumor, colorectal tumor, lung tumor, prostate tumor, ovarian tumor, pancreatic tumor, liver tumor, or bladder tumor.
  • the phthalocyanine dye is IRDyeTM 700DX. In some embodiments, the light has a wavelength of about 660 to 740 nm.
  • the moiety or biomolecule specifically binds a CTC antigen.
  • the CTC antigen is selected from the group consisting of epithelial cell adhesion molecule (EpCAM), cytokeratin 8, cytokeratin 18, cytokeratin 19, E-cadherin, fibronectin, vimentin, MUC1, Her2, Twist, E-selectin, HSPG, CD44, octreoate, and others.
  • the therapeutically effective agent is administered at the time of anticoagulant administration with heparin, sodium citrate, thrombin inhibitors, prostacyclin and other prostanoids or other effective anticoagulants.
  • un-bound therapeutically effective agent will be reduced or removed from blood via filtration or dialyzer or methods that involved molecular movement.
  • a method of extracorporeal treatment of cancer in a subject having circulating tumor cells comprises: (a) intravenously administering a therapeutically effective agent comprising a phthalocyanine dye conjugated to a targeting moiety that specifically binds to CTCs; (b) ex vivo irradiating the subject's blood with a light (e.g., wavelength of 660 to 740 nm) in an amount to effectively induce apoptosis, necrosis or autophagy in CTCs; and (c) re-introducing the irradiated blood into the subject, thereby treating cancer in the subject.
  • a light e.g., wavelength of 660 to 740 nm
  • step (b) and/or (c) are performed using an extracorporeal device.
  • the subject has undergone solid tumor resection.
  • the therapeutic agent is IRDye® 700DX.
  • the light has a wavelength of 660 to 740 nm.
  • the antibody specifically binds a CTC antigen.
  • the CTC antigen is selected from the group consisting of epithelial cell adhesion molecule (EpCAM), cytokeratin 8, cytokeratin 18, cytokeratin 19, E-cadherin, fibronectin, vimentin, MUC1, Her2, Twist, E-selectin, HSPG, CD44, octreoate, and others.
  • the therapeutically effective agent is administered at the time of anticoagulant administration with heparin, sodium citrate, thrombin inhibitors, prostacyclin and other prostanoids or other effective anticoagulants.
  • unbound therapeutically effective agent will be reduced or removed from blood via filtration or dialyzer or methods that involved molecular movement.
  • ex vivo irradiating is performed using an extracorporeal device.
  • a method of extracorporeal treatment of cancer in a subject having CTCs comprises: (a) administering a targeting agent comprising a magnetic particle conjugated to a biomolecule that specifically binds to CTCs; (b) ex vivo treatment of CTCs with an extracorporeal circuit to separate the particle-bound CTCs from blood stream with magnetic influence(s); and (c) re-introducing the treated blood into the subject, thereby mitigate the number of CTCs in the subject.
  • the treatment agent is introduced ex vivo through the extracorporeal device.
  • the subject has undergone solid tumor resection.
  • the antibody specifically binds a CTC antigen.
  • the CTC antigen is selected from the group consisting of epithelial cell adhesion molecule (EpCAM), cytokeratin 8, cytokeratin 18, cytokeratin 19, E-cadherin, fibronectin, vimentin, MUC1, Her2, Twist, E-selectin, HSPG, CD44, octreoate, and others.
  • the magnetic particle-targeted CTCs is removed or separated from blood via methods that involve molecular movement such as the influence of magnetic field(s).
  • a therapeutically effective composition comprising a therapeutically effective agent comprising a phthanlocyanine dye conjugated to a circulating tumor cell (CTC) targeting moiety or biomolecule that specifically binds to a CTC.
  • CTC circulating tumor cell
  • the phthalocyanine dye is IRDye® 700DX.
  • the targeting moiety or biomolecule specifically binds a CTC antigen.
  • the CTC antigen is selected from the group consisting of epithelial cell adhesion molecule (EpCAM), cytokeratin 8, cytokeratin 18, cytokeratin 19, E-cadherin, fibronectin, vimentin, MUC1, Her2, Twist, E-selectin, HSPG, CD44, octreoate, and others.
  • EpCAM epithelial cell adhesion molecule
  • cytokeratin 8 cytokeratin 18, cytokeratin 19, E-cadherin, fibronectin, vimentin, MUC1, Her2, Twist, E-selectin, HSPG, CD44, octreoate, and others.
  • FIG. 1 is a schematic illustration of an exemplary embodiment in which the CTC extracorporeal photodynamic treatment is performed in the extracorporeal circuit.
  • FIG. 2 illustrates an exemplary embodiment of the methods with CTC targeting magnetic particles which attaches to CTCs and renders the removal of CTCs with magnetic influence (e.g., a magnetic field).
  • CTC targeting magnetic particles which attaches to CTCs and renders the removal of CTCs with magnetic influence (e.g., a magnetic field).
  • FIGS. 3A-E show a reduction in the number of targeted cancer cells after exposure to irradiating light at 8 J/cm 2 or 16 J/cm 2 .
  • FIGS. 3A-C show control data and FIGS. 3D-E show exposure to 8 J/cm 2 or 16 J/cm 2 , respectively.
  • FIGS. 4A-D show a reduction in the number of targeted cancer cells after exposure to irradiating light at 670 nm to 700 nm at 8 J/cm 2 or 16 J/cm 2 was made through 1 mm whole blood.
  • FIGS. 4A-B present control data and FIGS. 4C-D show exposure to 8 J/cm 2 or 16 J/cm 2 , respectively.
  • FIGS. 5A-B show the IRDye® 700DX-EGF probe binding to A431 cells at two concentrations for two different time periods.
  • A431 cells received a peristaltic flow of 1.36 mL/min of IRDye® 700DX-EGF at a concentration of 0.2 ⁇ M for 15 min ( FIG. 5A ).
  • A431 cells received a peristaltic flow of 1.36 mL/min of IRDye®700DX-EGF at a concentration of 0.5 ⁇ M for 5 min ( FIG. 5B ).
  • FIGS. 6A-6D show images of A431 cells incubated for 5 minutes with variable concentrations of IRDye 700DX®-EGF and then irradiated at 4 J/cm 2 .
  • FIG. 6A shows the cells during the incubation of 0.5 ⁇ M of probe and
  • FIG. 6B shows the cells after irradiation.
  • FIG. 6C shows the cells incubated with 2 ⁇ M of probe.
  • FIG. 6D shows these cells after irradiation.
  • FIGS. 7A-7D provides images of A431 cells incubated for 10 minutes with variable concentrations of IRDye 700DX®-EGF and then irradiated at 16 J/cm 2 .
  • Cells that were incubated with 0.5 ⁇ M of probe are shown in FIG. 7A .
  • FIG. 7B shows these cells after irradiation.
  • FIG. 7C shows cells treated with 2 ⁇ M of probe and
  • FIG. 7D shows the cells after irradiation treatment.
  • FIG. 8 illustrates that the percent cell vitality was lower for irradiation treatments of 16 J/cm 2 (e.g., treatments 3, 4, 7 and 8) compared to those of 4 J/cm 2 . Within the parameters tested, cell vitality was independent of probe concentration and probe incubation times.
  • FIGS. 9A-C provides data of the statistical analysis performed.
  • FIG. 9A shows the Box-Cox plot indicating that no transformation of data was required.
  • FIG. 9B shows the normal probability plot of residuals that indicates that the residuals followed a normal distribution and were a good fit.
  • FIG. 9C shows the ANOVA analysis.
  • FIG. 10 provides a graph of the percent cell vitality of tumor cells treated with IRDye® 700DX-EGF or IRDye® 700DX-panitumumab and irradiated at 24 J/cm 2 . The cells were incubated for 5 minutes, 10 minutes or 20 minutes with the probe.
  • FIGS. 11A-C provides images of the cells after irradiation at 24 J/cm 2 .
  • the cells exhibited morphological blebbing which is associated with apoptosis and/or necrosis (see, white arrows).
  • the present invention relates to compositions and methods for the elimination of CTCs circulating in the blood of an individual. More particularly, the invention involves the use of a continuous-flow, extracorporeal device that treats the cells with IRDye®-targeting agents or magnetic particle-targeting agent to either trigger CTC cell death or enable the removal of CTCs from the blood stream before returning the treated blood to the body.
  • Cell death of CTCs can be induced with an IRDye®700DX-targeting agent and the appropriate light exposure.
  • the CTCs can be removed from the blood using a magnetic particle-targeting agent and a magnetic influence.
  • CTC targeting moiety refers to any compound, molecule, or fragment thereof that can specifically bind to to the surface of a circulating tumor cell (CTC), e.g., any component present on the surface of a CTC, and/or tumor cell matter, e.g., any matter or component thereof that is derived, originated, or secreted from a tumor cell.
  • CTC circulating tumor cell
  • Molecules that can be used as CTC targeting moieties include, but are not limited to, peptides, polypeptides, proteins, peptidomimetics, ligands, antigens, antibodies, antibody fragments (e.g., antigen binding fragments of antibodies), nanobodies, Affibodies®, diabodies, minibodies, carbohydrate-binding protein, e.g., a lectin, glycoproteins, glycoprotein-binding molecules, amino acids, carbohydrates (including mono-, di-, tri- and poly-saccharides), lipids, steroids, hormones, lipid-binding molecules, cofactors, nucleosides, nucleotides, nucleic acids (e.g., DNA or RNA, analogues and derivatives of nucleic acids, or aptamers), peptidoglycans, lipopolysaccharides, small molecules, and any combinations thereof.
  • carbohydrate-binding protein e.g., a lect
  • antibody refers to a polypeptide comprising at least a light chain or heavy chain immunoglobulin variable region which specifically recognizes and binds an epitope of an antigen, such as a tumor-specific protein.
  • Antibodies are composed of a heavy and a light chain, each of which has a variable region, termed the variable heavy (V H ) region and the variable light (V L ) region. Together, the V H region and the V L region are responsible for binding the antigen recognized by the antibody.
  • Antibodies include intact immunoglobulins and the variants and portions of antibodies well known in the art, such as Fab fragments, Fab′ fragments, F(ab)′ 2 fragments, single chain Fv proteins (“scFv”), and disulfide stabilized Fv proteins (“dsFv”).
  • scFv protein is a fusion protein in which a light chain variable region of an immunoglobulin and a heavy chain variable region of an immunoglobulin are bound by a linker, while in dsFvs, the chains have been mutated to introduce a disulfide bond to stabilize the association of the chains.
  • the term also includes genetically engineered forms such as chimeric antibodies (for example, humanized murine antibodies), heteroconjugate antibodies (such as, bispecific antibodies). See also, Pierce Catalog and Handbook, 1994-1995 (Pierce Chemical Co., Rockford, Ill.); Kuby, J., Immunology, 3rd Ed., W.H. Freeman & Co., New York, 1997.
  • the term “IRDye® 700DX” or “IR700” refers to a dye having the preferred NHS ester linkage to allow for conjugation to a CTC targeting moiety.
  • the CTC targeting moiety such as an antibody has a primary amine (e.g., an amino group) wherein the NHS ester and the amino group react to form an amide bond, linking the targeting moiety such as an antibody to 700DX.
  • the NHS ester IRDye® 700DX has the following formula:
  • the dye is commercially available from LI-COR (Lincoln, Nebr.).
  • Amino-reactive IRDye® 700DX is a relatively hydrophilic dye and can be covalently conjugated with an antibody using the NHS ester of IRDye® 700DX.
  • Other variations of IRDye 700Dx are disclosed in U.S. Pat. No. 7,005,518 (incorporated herein by reference), and those too are useful in the present invention.
  • the carboxylate derivative has the following name and structure, silicate(5-), bis[N[3-[(hydroxy-.kappa.O)dimethylsilyl]propyl]-3-sulfo-N,N-bis(3-sulfopropyl)-1-propanaminiumato(4-)][6-[[[3-[(29H,31H-phthalocyanin-yl-.kappa.N29,.kappa.N30,.kappa.N31,.kappa.N32)oxy]propoxy]carbonyl]amino]hexanoato(3-)]-, sodium (1:5); CAS Registry Number: [1623074-46-3]:
  • photodynamic therapy refers to a molecular targeted therapy that utilizes a target-specific photosensitizer agent, based on a near infrared (NIR) phthalocyanine dye, IRDye® 700DX, conjugated to a targeting moiety that specifically bind to a cell surface protein.
  • NIR near infrared
  • IRDye® 700DX conjugated to a targeting moiety that specifically bind to a cell surface protein.
  • the cell surface protein such as EpCam is found specifically on circulating tumor cells, and thus photodynamic therapy can be used to kill such cells.
  • Cell death of the cells can be induced when the IRDye® 700DX-anti-EpCam antibody binds to the cells and the cells are irradiated with the proper excitation light.
  • the cytotoxic agent is produced by one of the two different processes called Type I or Type II PDT pathways. Type I generates radicals and Type II generates singlet oxygen. Both radicals and singlet oxygen cause oxidative destruction of tissues
  • Non-targeted options for PDT include sensitizers, porphyrins, chlorophylls and dyes.
  • Non-limiting examples of useful photosensitizers include aminolevulinic acid (ALA), silicon phthalocyanine Pc 4, m-tetrahydroxyphenylchlorin (mTHPC), mono-L-aspartyl chlorine 6 (NPe6), and methylene blue.
  • ALA aminolevulinic acid
  • mTHPC silicon phthalocyanine Pc 4
  • NPe6 mono-L-aspartyl chlorine 6
  • methylene blue methylene blue
  • Commercially photosensitizers available for clinical use include Allumera®, Photofrin®, Visudyne®, Levulan®, Foscan®, Metvix®, Hexvix®, Cysview®, and Laserphyrin®.
  • photosensitizers in development include Antrin®, Photochlor®, Photosens, Photrex®, Lumacan®, Cevira®, Visonac®, BF-200 ALA®, Amphinex®, and Azadipyrromethene®.
  • PDT agents include halogenated compounds, such as those described in, e.g., U.S. Patent Publication No.
  • 2013/0231604 near-infrared light triggered upconversion nanoconstruct, such as those described in, e.g., Cui et al., ACS Nano, 2013, 7 (1), 676-688; hyaluronic acid-conjugated grapheme oxide/photosensitizer nanohybrids, such as those described in, e.g., Li et al., J. Mater. Chem. B, 2013, 1, 1678-1686, and aptamer-guided G-Quadruplex DNA carriers, such as those described in, e.g., Yuan et al., Angew. Chem. Int. Ed., 52: 13965-13969.
  • near-infrared light triggered upconversion nanoconstruct such as those described in, e.g., Cui et al., ACS Nano, 2013, 7 (1), 676-688
  • terapéuticaally effective amount refers to an amount of a composition that alone, or together with an additional therapeutic agent(s) (such as a chemotherapeutic agent) is sufficient to achieve a desired effect in a subject, or in a cell, being treated with the composition.
  • the effective amount of the therapeutic composition can be dependent on several factors, including, but not limited to the subject or cells being treated, the particular therapeutic agent, and the manner of administration of the therapeutic composition.
  • a therapeutically effective amount or concentration is sufficient to prevent advancement (such as metastasis), delay progression, or to cause regression of a disease, or which is capable of reducing symptoms caused by the disease, such as cancer.
  • a therapeutically effective amount or concentration is sufficient to increase the survival time of a patient with a circulating tumor cell.
  • extractor refers to an instrument that receives blood that is removed from a patient, processes (e.g., filters, purifies, treats, administers therapeutic agents to, etc.) the blood, and then returns the blood to the patient.
  • processes e.g., filters, purifies, treats, administers therapeutic agents to, etc.
  • magnetic particles includes beads, microbeads, and particles that a magnetic or paramagnetic.
  • subject typically refers to humans, but also to other animals including, e.g., other primates, rodents, canines, felines, equines, ovines, porcines, and the like.
  • the methods provided herein can be used to treat a cancer patient post tumor resection (e.g., tumor excision by surgery) or treatment by reducing the circulating tumor cells (CTCs) in the blood, and thus, reducing the chance of metastatic spread.
  • Photodynamic therapy utilizes photosensitizers (e.g., photosensitizing agents or drugs) and light exposure to kill cancer cells.
  • photosensitizers e.g., photosensitizing agents or drugs
  • the photosensitizing agent, porfimer sodium e.g., Photofrin® is FDA approved for use in PDT to treat the symptoms of esophageal cancer and non-small cell lung cancer.
  • Aminnolevulini acid (ALA or Levulan®) and methyl ester of ALA (Metvixia® cream) are FDA approved for skin or topical treatment for PDT. Most photosensitizing agents are not targeted and require irradiation of the whole body or a large region, which can result in unwanted cell death of normal tissues.
  • an extracorporeal device that can circulate blood containing CTC targeted agents and to either induce CTC cell death (e.g., apoptosis, necrosis or autophagy) or to separate the CTCs from the blood returning to the body.
  • CTC cell death e.g., apoptosis, necrosis or autophagy
  • the cell death is induced by photodynamic therapy method for CTCs that employs an IRDye®-targeting agent that can be excited by an irradiating light of a wavelength from 660 nm to about 740 nm.
  • the irradiated blood can be returned (e.g., reintroduced) to the subject where the subject's immune system can recognize the apoptotic and/or necrotic cells and target them for removal.
  • the extracorporeal device is to circulate blood outside the body for the treatment of the agent targeted CTCs.
  • targeted photosensitizing agents such as IRDye® 700DX-CTC moieties.
  • Any targeting moiety e.g., an antibody or fragment thereof, nanobody, Affibody®, diabody, minibody, antigen, ligand, protein, peptide, carbohydrate, nucleic acids, or small molecule
  • Any targeting moiety e.g., an antibody or fragment thereof, nanobody, Affibody®, diabody, minibody, antigen, ligand, protein, peptide, carbohydrate, nucleic acids, or small molecule
  • the targeting moiety is specific for a protein expressed on the cell surface of a CTC.
  • the cell surface protein can be selectively expressed on the surface of CTCs, and not other cells such as normal cells.
  • the cell surface protein is epithelial cell adhesion molecule (EpCAM), cytokeratin 8, cytokeratin 18, cytokeratin 19, E-cadherin, fibronectin, vimentin, MUC1, Her2, Twist, E-selectin, HSPG, CD44, octreoate, and others.
  • EpCam antibodies are available from, e.g., Abeam® (Cambridge, Mass.), Cell Signaling Technology® (Danvers, Mass.), Santa Cruz Biotechnology® (Santa Cruz, Calif.), and other companies.
  • the generation and selection of antibodies not already commercially available for targeting circulating tumor cells in accordance with the present invention can be accomplished several ways. For example, one way is to express and/or purify a polypeptide of interest (i.e., antigen) using protein expression and purification methods known in the art, while another way is to synthesize the polypeptide of interest using solid phase peptide synthesis methods known in the art. See, e.g., Guide to Protein Purification , Murray P. Deutcher, ed., Meth. Enzymol ., Vol. 182 (1990); Solid Phase Peptide Synthesis , Greg B. Fields, ed., Meth. Enzymol ., Vol. 289 (1997); Kiso et al., Chem.
  • binding fragments or Fab fragments which mimic (e.g., retain the functional binding regions of) antibodies can also be prepared from genetic information by various procedures. See, e.g., Antibody Engineering: A Practical Approach , Borrebaeck, Ed., Oxford University Press, Oxford (1995); and Huse et al., J. Immunol., 149:3914-3920 (1992).
  • the CTC targeting agent (e.g., CTC targeting moiety) can be conjugated to a phthalocyanine dye, IRDye® 700DX (LI-COR, Lincoln, Nebr.).
  • CTC targeting moieties are labeled with IRDye® 700DX according to the manufacturer's protocols and kits.
  • Detailed descriptions of methods for producing IRDye® 700DX-conjugates are found in, e.g., Kovar et al, Biochemistry—Faculty Publications, 2007, paper 9; Mitsunaga et al., Nature Medicine, 2011, 17:1685-1691; Peng et al., Proceedings of SPIE, 2006, 6097; U.S. Pat. Nos. 7,005,518 and 8,524,239; and U.S. Patent Application Publication No. 2013/0336995, the disclosures of each are herein incorporated in their entirety for all purposes.
  • the IRDye®700DX-CTC moiety can be administered to the subject's blood in the blood circuit of the extracorporeal device.
  • the targeting agent is injected into the blood that has exited the subject prior to treatment by the excitation light.
  • the dose of IRDye® 700DX-CTC moiety or biomolecle can be removed or cleared from the blood before returning to the subject.
  • the removal or clearance methods can be mechanisms involved in molecular movement or attachment to isolate the agent from the blood stream so that the returning blood contains minimal amount of the therapeutic agent.
  • the IRDye® 700DX-CTC moiety or biomolecule can be administered systemically using any method known in the art, for example to subjects having a tumor, such as a cancer, or who has had tumor resection (e.g., tumor removal, for example, by surgery).
  • a tumor such as a cancer
  • tumor resection e.g., tumor removal, for example, by surgery
  • any method of systemic administration of the disclosed IRDye®700DX-CTC moiety or biomolecule can be used. Such methods may include for example, the use of catheters or implantable pumps to provide continuous infusion over a period of several hours to several days into the subject in need of treatment. Other methods include direct injection or infusion into the blood.
  • the IRDye® 700DX-CTC moiety or biomolecule can be administered systemically, for example intravenously, intramuscularly, subcutaneously, intradermally, intraperitoneally, subcutaneously, or orally, to a subject having CTCs.
  • the dosages of IRDye® 700DX-CTC moiety to be administered to a subject will depend on the nature of the composition and its active ingredients and its unwanted side effects (e.g., immune response against the moiety or biomolecule), the subject being treated and the type of condition being treated and the manner of administration.
  • the dose will be a therapeutically effective amount, such as an amount sufficient to achieve a desired biological effect, for example an amount that is effective to reduce the number of CTCs in the subject, eliminate the CTCs, or decrease the chance of metastasis spread.
  • exemplary dosages for administration to a subject for a single treatment can range from about 0.5 to 100 mg/60 kg of body weight, about 1 to 100 mg/60 kg of body weight, about 1 to 50 mg/60 kg of body weight, about 1 to 20 mg/60 kg of body weight, for example about 1 or 2 mg/60 kg of body weight.
  • Treatments with the IRDye®700 DX-CTC moiety or biomolecule can be completed in a single day, or may be done repeatedly on multiple days with the same or a different dosage. Repeated treatments may be done on the same day, on successive days, or every 1-3 days, every 3-7 days, every 1-2 weeks, every 2-4 weeks, every 1-2 months, or at even longer intervals.
  • the cells are contacted with one or more IRDye®700DX-CTC moiety or biomolecule, they are removed from the patient's body using an extracorporeal device wherein they are irradiated.
  • blood containing the targeted cells is removed from the patient using a dialysis-like device and exposed to an irradiating light, e.g., at a wavelength of 660-740 nm.
  • the cells in the blood are irradiated with a therapeutic dose of radiation at a wavelength of about 660-740 nm, e.g., about 660-700 nm, 670-690 nm, 660-680 nm. In preferred embodiments, the cells are irradiated with a therapeutic dose of radiation at a wavelength of about 680 nm.
  • the cells are irradiated at a dose of at least 1 J cm ⁇ 2 , e.g., at least 1 J cm ⁇ 2 , at least 10 J cm ⁇ 2 , at least 30 J cm ⁇ 2 , at least 50 J cm ⁇ 2 , at least 100 J cm ⁇ 2 , or at least 500 J cm ⁇ 2 .
  • the irradiating light is applied at, for example, 1-1000 J cm ⁇ 2 , 1-500 J cm ⁇ 2 , 10-100 J cm ⁇ 2 , or 10-50 J cm ⁇ 2 .
  • the targeted cells in the blood can be irradiated one or more times.
  • irradiation can be completed in a single day, or may be done repeatedly on multiple days with the same or a different dosage (such as irradiation at least 2 different times, 3 different times, 4 different times, 5 different times or 10 different times). Repeated irradiations may be done on the same day, on successive days, or every 1-3 days, every 3-7 days, every 1-2 weeks, every 2-4 weeks, every 1-2 months, or at even longer intervals.
  • FIG. 1 An exemplary embodiment of the method and the device 100 is provided in FIG. 1 .
  • the method and device provided herein can be used for performing extracorporeal CTC photodynamic therapy on a patient with circulating tumor cells using an extracorporeal circuit 110 , and a radiation chamber 150 housed in or separately from the extracorporeal device 100 .
  • Blood is drawn from the patient, bearing an intravenous catheter, an arteriovenous fistula (AV) or a synthetic graft, etc., through the blood line 120 and transported to the fluid circuit 110 .
  • a pump system 130 comprising pumps (e.g., peristaltic pumps) and tubing for the transport of flow from and to different unit sections.
  • the blood pressure, temperature, pH, and/or other parameters are monitored.
  • An anticoagulant can be added via, for example, injection to the blood in the circuit to prevent blood clotting.
  • the IRDye® 700-CTC targeting agent e.g., IRDye® 700DX-CTC moiety or biomolecule
  • the blood including the IRDye® 700DX labeled CTCs enter a phototherapy chamber 150 where the blood is exposed to irradiating light in the illumination circuit. The treated blood exits the phototherapy chamber 150 and is moving toward blood reintroducing line 121 .
  • the therapeutic agent e.g., the unbound therapeutic agent
  • the clearance chamber can be a dialyzer, a supernatant remover, a filter, or other physical methods for the clearance of the agent molecules.
  • a light source provides an excitation light at a wavelength of about 660 nm to about 740 nm to the blood and labeled target CTCs as they pass through the phototherapy chamber. Exposure to the irradiating light induces the CTCs to undergo cell death, such as apoptosis, necrosis or autophagy.
  • FIG. 2 Another exemplary embodiment of the method and the device 200 is provided in FIG. 2 .
  • the methods herein can be used for performing extracorporeal CTC removal with the extracorporeal circuit 210 to reduce the number of CTCs before reintroducing the cleaned blood to the body.
  • Blood is drawn from the patient through blood line 220 and transported to the extracorporeal circuit 210 .
  • a pump system 230 comprising pump(s) (e.g. peristaltic pumps) and tubing for the transport of flow from and to different unit sections.
  • the blood pressure, temperature, pH, and/or other parameters can be monitored.
  • Chosen anticoagulant can be added via injection to the blood in the circuit to prevent blood clotting.
  • the magnetic particle targeting agent (e.g., magnetic beads-CTC moiety) is added to the blood via the agent administration unit 240 with controlled flow rate and/or flow pressure.
  • the blood including the targeted CTCs enter a magnetic influence chamber 250 where magnetic field is applied to the flow circuit.
  • the magnetic field retains magnetic particle targeted CTCs from the blood flow before returning to the body through the reintroducing line 221 .
  • the agent remnants (e.g., the unbound agents) are removed or reduced via the agent clearance chamber 270 .
  • the clearance chamber can be a filter, a dialyzer, a supernatant remover, or other methods for the clearance of agent molecules.
  • This example illustrates the application of photodynamic therapy using an IRDye® 700DX-targeting agent (e.g., EGF-700DX) and photoactivating light to kill targeted cells.
  • an IRDye® 700DX-targeting agent e.g., EGF-700DX
  • Cancer cells that overexpress the EGF receptor (e.g., A431 cells) were seeded in an in vitro culture system. The cells were incubated with the targeting agent EGF-700DX and exposed to irradiating light at a wavelength of 690 nm and at 8 J/cm 2 or 16 J/cm 2 .
  • FIG. 3 shows a reduction in the number of targeted cells after exposure to irradiating light at 8 J/cm 2 or 16 J/cm 2 .
  • FIGS. 3A-E show a reduction in the number of targeted cancer cells after exposure to irradiating light at 8 J/cm 2 or 16 J/cm 2 .
  • FIGS. 3A-C are control data and FIGS. 3D-E show exposure to 8 J/cm 2 or 16 J/cm 2 , respectively.
  • FIG. 3E shows significant morphology changes in cells treated with EGF-700DX and irradiating light at 16 J/cm 2 .
  • FIG. 4 shows a reduction in the number of targeted cells in blood after exposure to irradiating light at 670 nm to 700 nm at 8 J/cm 2 or 16 J/cm 2 .
  • FIGS. 4A-D shows a reduction in the number of targeted cancer cells in blood after exposure to irradiating light at 670 nm to 700 nm at 8 J/cm 2 or 16 J/cm 2 .
  • FIGS. 4A-B are control data and FIGS. 4C-D show exposure to 8 J/cm 2 or 16 J/cm 2 , respectively.
  • the targeting conjugate was flowed over the cells in a closed peristaltic pump setup at two different concentrations for two different time periods. Binding was evaluated at this step in the testing phase. No irradiation was added at this point.
  • FIGS. 5A and 5B show that EGF-700DX successfully bound to the cultured cells.
  • the flow rate of the conjugate concentration was 1.36 mL/min.
  • A431 cells received either EGF-700DX (0.2 ⁇ M) for 15 min ( FIG. 5A ) or EGF-700DX (0.5 ⁇ M) for 5 min ( FIG. 5B ).
  • this example shows that cancer cells were killed by labeling them with an IRDye®700DX-targeting agent (e.g., EGF-700DX) and exposing the labeled cells to photoactivating light. Furthermore, the presence of blood with the labeled cells did not affect the photodynamic method of irradiation. Additionally, the results illustrate that the IRDye® 700DX-targeting agent effectively binds to stationary cells within minutes.
  • an IRDye®700DX-targeting agent e.g., EGF-700DX
  • cancer cells that overexpress EGF e.g., A431 cells
  • IRDye® 700DX-EGF probe at the test concentration and at a flow rate of 1.36 mL/min.
  • the cells were washed to remove any unbound probe prior to irradiation.
  • images of the cells were captured to determine the location of the probe and the extent of probe binding.
  • the cells were then irradiated and imaged to identify morphology changes. 24 hours after irradiation, cell vitality (e.g., cell count and cell viability) was assessed using the NucleoCounter® NC-3000TM assay (Chemometec, Aller ⁇ d, Denmark).
  • the data shows that the IRDye®700DX-EGF probe effectively bound to the cell surface of the EGF-positive cells after a brief incubation period. After incubation for 5 minutes with 0.5 ⁇ M probe ( FIG. 6A ) or 2.0 ⁇ M probe ( FIG. 6C ), the cells were irradiated at 4 J/cm 2 ( FIGS. 6B and 6D , respectively). No visual difference was observed between the treatments.
  • the cells were incubated for 10 minutes with either 0.5 ⁇ M probe ( FIG. 7A ) or 2.0 ⁇ M probe ( FIG. 7C ) and irradiated at 16 J/cm 2 ( FIGS. 7B and 7D , respectively). Some change in morphology was detected immediately after irradiation. Apoptosis and/or necrosis was assessed 24 hours later using the cell vitality assay. The data shows that cell death was higher (e.g., lower % cell vitality) for treatments conducted at 16 J/cm 2 , such as for treatments 3, 4, 7, and 8 ( FIG. 8 ).
  • this example shows the use of a photodynamic therapeutic method for initiating cell death in cancer cells overexpressing the EGF receptor.
  • the experiments showed that the IRDye® 700DX-EGF probe selectively targeted the cancer cells which were then irradiated by a photoactivating light.
  • the cell vitality assay showed that some of the treated cells underwent cell death.
  • IRDye® 700DX-EGF probe and the IRDye® 700DX-panitumumab probe can induce cell death in A431 cells which are human epithelial cancer cells that overexpress the EGF receptor.
  • EGF is the ligand for the EGF receptor and panitumumab is a fully human monoclonal antibody specific to the receptor.
  • IRDye® 700DX targeting probes such as those based on proteins and antibodies, were able to target select cancer cells.
  • the probe-bound cells underwent induced cell death upon photoactivation of the probe.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Biomedical Technology (AREA)
  • Optics & Photonics (AREA)
  • Physics & Mathematics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Cardiology (AREA)
  • Anesthesiology (AREA)
  • Hematology (AREA)
  • Dermatology (AREA)
  • Biochemistry (AREA)
  • Immunology (AREA)
  • Cell Biology (AREA)
  • Toxicology (AREA)
  • Radiology & Medical Imaging (AREA)
  • Biophysics (AREA)
  • Pathology (AREA)
  • Urology & Nephrology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
US14/728,204 2014-06-02 2015-06-02 Treatment of circulating tumor cells using an extracorporeal device Abandoned US20150343060A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US14/728,204 US20150343060A1 (en) 2014-06-02 2015-06-02 Treatment of circulating tumor cells using an extracorporeal device

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201462006790P 2014-06-02 2014-06-02
US201462017165P 2014-06-25 2014-06-25
US201462066807P 2014-10-21 2014-10-21
US201462082052P 2014-11-19 2014-11-19
US14/728,204 US20150343060A1 (en) 2014-06-02 2015-06-02 Treatment of circulating tumor cells using an extracorporeal device

Publications (1)

Publication Number Publication Date
US20150343060A1 true US20150343060A1 (en) 2015-12-03

Family

ID=54700548

Family Applications (5)

Application Number Title Priority Date Filing Date
US14/728,304 Active 2035-12-28 US10588972B2 (en) 2014-06-02 2015-06-02 Phthalocyanine probes and uses thereof
US14/728,247 Active US10064943B2 (en) 2014-06-02 2015-06-02 Therapeutic and diagnostic probes
US14/728,204 Abandoned US20150343060A1 (en) 2014-06-02 2015-06-02 Treatment of circulating tumor cells using an extracorporeal device
US16/046,748 Abandoned US20180339048A1 (en) 2014-06-02 2018-07-26 Therapeutic and Diagnostic Probes
US16/751,850 Abandoned US20200179514A1 (en) 2014-06-02 2020-01-24 Phthalocyanine probes and uses thereof

Family Applications Before (2)

Application Number Title Priority Date Filing Date
US14/728,304 Active 2035-12-28 US10588972B2 (en) 2014-06-02 2015-06-02 Phthalocyanine probes and uses thereof
US14/728,247 Active US10064943B2 (en) 2014-06-02 2015-06-02 Therapeutic and diagnostic probes

Family Applications After (2)

Application Number Title Priority Date Filing Date
US16/046,748 Abandoned US20180339048A1 (en) 2014-06-02 2018-07-26 Therapeutic and Diagnostic Probes
US16/751,850 Abandoned US20200179514A1 (en) 2014-06-02 2020-01-24 Phthalocyanine probes and uses thereof

Country Status (7)

Country Link
US (5) US10588972B2 (ja)
EP (2) EP3148583B1 (ja)
JP (3) JP6741599B2 (ja)
CN (2) CN106573054B (ja)
AU (1) AU2015271830B2 (ja)
CA (1) CA2950299A1 (ja)
WO (2) WO2015187651A1 (ja)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10064943B2 (en) 2014-06-02 2018-09-04 Li-Cor, Inc. Therapeutic and diagnostic probes
US10538590B2 (en) 2010-07-09 2020-01-21 The United States Of America, As Represented By The Secretary, Dept. Of Health And Human Services Photosensitizing antibody-fluorophore conjugates
US10830678B2 (en) 2014-08-08 2020-11-10 The United States Of America, As Represented By The Secretary, Department Of Health And Human Serv Photo-controlled removal of targets in vitro and in vivo
US11013803B2 (en) 2015-08-07 2021-05-25 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Near infrared photoimmunotherapy (NIR-PIT) of suppressor cells to treat cancer
US11141483B2 (en) 2015-08-18 2021-10-12 Rakuten Medical, Inc. Methods for manufacturing phthalocyanine dye conjugates and stable conjugates
US11147875B2 (en) 2015-08-18 2021-10-19 Rakuten Medical, Inc. Compositions, combinations and related methods for photoimmunotherapy
US11678825B2 (en) * 2018-10-04 2023-06-20 Fenwal, Inc. Methods and systems for collecting samples in a photopheresis procedure
US11827721B2 (en) 2018-03-02 2023-11-28 Universität Zürich and ETH Zurich Bioconjugates of antibodies and functionalized magnetic nanoparticles

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016111915A1 (en) * 2015-01-06 2016-07-14 De Haas Anthony H Near-infrared fluorescent surgical dye markers
EP3405550B1 (en) 2016-01-19 2021-04-21 Nanosys, Inc. Method of producing inp quantum dots with gap and alp shells
WO2017132639A1 (en) * 2016-01-30 2017-08-03 The Board Of Trustees Of The Leland Stanford Junior University Light-activated anchoring of therapeutic factors to tissues
CN107412794B (zh) * 2017-04-17 2019-01-04 中国医学科学院北京协和医院 双靶点显像分子探针及其制备方法和应用
GB201710097D0 (en) * 2017-06-23 2017-08-09 Univ Ulster A sensitizer - peptide conjugate
JP7216435B2 (ja) * 2018-03-09 2023-02-01 学校法人慈恵大学 血管を標的とする抗体と光増感剤とのコンジュゲート
US20210228750A1 (en) * 2018-04-30 2021-07-29 Bar-Ilan University Polymeric core-shell particles
WO2020032165A1 (ja) 2018-08-08 2020-02-13 国立大学法人 東京大学 ビオチン改変二量体とフタロシアニン染料とのコンジュゲート
CN109232906A (zh) * 2018-09-20 2019-01-18 福建师范大学 多氟烷基轴向取代硅（iv）酞菁-碳纳米管纳米超分子体系及其制备方法与应用
US20210386782A1 (en) * 2018-10-18 2021-12-16 The Brigham And Women`S Hospital, Inc. Near Infrared Photoimmunotherapy
CA3136294A1 (en) * 2019-04-10 2020-10-15 Coralluma Llc. Ir700 nanocompositions for cardiac therapies and applications
CN115003679A (zh) * 2020-02-05 2022-09-02 国立大学法人东京大学 酞菁染料与抗体或肽的缀合物
JP2021129555A (ja) * 2020-02-18 2021-09-09 株式会社島津製作所 細胞精製装置および細胞精製方法
US20240190994A1 (en) 2021-03-25 2024-06-13 The University Of Tokyo Fusion protein between antigen-binding molecule and streptavidin variant
CN113512089B (zh) * 2021-06-30 2023-06-13 兰州大学 一种水溶性量子点的多肽稳定剂及应用
JPWO2023008515A1 (ja) 2021-07-29 2023-02-02
IL312728A (en) 2021-11-30 2024-07-01 Daiichi Sankyo Co Ltd Antibodies masked in protease-wells

Citations (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020114793A1 (en) * 1999-04-20 2002-08-22 Edelson Richard Leslie Methods for inducing the differentiation of monocytes into functional dendritic cells and immunotherapeutic compositions including such dendritic cells
US20030139466A1 (en) * 2001-11-29 2003-07-24 Peritt David L. Methods for pretreating a subject with extracorporeal photopheresis
US20050112131A1 (en) * 2002-03-25 2005-05-26 Brian Pogue Methods of adjuvant photodynamic therapy to enhance radiation sensitization
US20060134001A1 (en) * 2002-07-12 2006-06-22 Frangioni John V Conjugated infrared fluorescent substances for detection of cell death
WO2007070680A2 (en) * 2005-12-16 2007-06-21 The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Optically detectable probes for identification and treatment of tumors
US20080193431A1 (en) * 2003-11-14 2008-08-14 University Of Pennsylvania Activatable photodynamic therapy agents
US20090156976A1 (en) * 2007-03-01 2009-06-18 Martin Korbling Devices and Methods for Extracorporeal Ablation of Circulating Cells
US20100216226A1 (en) * 2009-02-25 2010-08-26 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Device, system, and method for controllably reducing inflammatory mediators in a subject
US20120010558A1 (en) * 2010-07-09 2012-01-12 Services, National Institutes of Health Photosensitizing antibody-fluorophore conjugates
US20120228568A1 (en) * 2011-03-10 2012-09-13 Joseph Alfred Leon Nail/Bolt Slide Hammer Extractor
US20130039860A1 (en) * 2010-10-20 2013-02-14 Li-Cor, Inc. Fluorescent imaging with substituted cyanine dyes
WO2013009475A9 (en) * 2011-07-11 2013-03-07 The United States Of America, As Represented By The Secretary, Department Of Health & Human Services Photosensitizing antibody-phuorophore conjugates
US20130131423A1 (en) * 2011-04-12 2013-05-23 Tianxin Wang Methods to detect and treat diseases
US20140161725A1 (en) * 2011-09-10 2014-06-12 Arizona Board Of Regents On Behalf Of The University Of Arizona Molecular Imaging of Cancer Cells In Vivo
US8889835B2 (en) * 2005-04-06 2014-11-18 Immunomedics, Inc. Polymeric carriers of therapeutic agents and recognition moieties for antibody-based targeting of disease sites
US20160228568A1 (en) * 2013-09-18 2016-08-11 Aura Biosciences, Inc. Virus-like particle conjugates for diagnosis and treatment of tumors

Family Cites Families (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3672292A (en) * 1970-09-22 1972-06-27 Vacu Blast Corp Blast-room for abrasive blasting system
US6667156B2 (en) 1995-12-27 2003-12-23 Uab Research Foundation Diagnosis and treatment of neuroectodermal tumors
US7230088B2 (en) * 2001-07-03 2007-06-12 Mallinckrodt, Inc. Compounds for dual photodiagnosis and therapy
US7597878B2 (en) 2000-09-19 2009-10-06 Li-Cor, Inc. Optical fluorescent imaging
DE60116510T2 (de) 2000-09-19 2006-07-13 Li-Cor, Inc., Lincoln Cyaninfarbstoffe
US20030105299A1 (en) 2001-10-17 2003-06-05 Mallinckrodt Inc. Carbocyanine dyes for tandem, photodiagnostic and therapeutic applications
US7597876B2 (en) 2007-01-11 2009-10-06 Immunomedics, Inc. Methods and compositions for improved F-18 labeling of proteins, peptides and other molecules
US7005518B2 (en) 2002-10-25 2006-02-28 Li-Cor, Inc. Phthalocyanine dyes
US7119168B2 (en) 2002-11-18 2006-10-10 Bioprospecting Nb Inc. Paralytic peptide for use in neuromuscular therapy
ES2545533T3 (es) 2004-11-01 2015-09-11 The Regents Of The University Of California Composiciones y métodos para modificación de biomoléculas
CN100362103C (zh) * 2004-12-21 2008-01-16 苏州大学 人表皮生长因子核酸序列及其应用
US20060204443A1 (en) 2005-03-11 2006-09-14 The Government Of The Usa As Represented By The Secretary Of The Dept. Of Health & Human Services Methods for tumor treatment using dendrimer conjugates
US8227621B2 (en) 2005-06-30 2012-07-24 Li-Cor, Inc. Cyanine dyes and methods of use
WO2008005942A2 (en) 2006-06-30 2008-01-10 The Govt. Of The Usa As Represented By The Secretary Of The Dept. Of Health And Human Services. Activatable probes and methods of use
AU2008251615B2 (en) * 2007-05-08 2014-09-18 The United States of America, as represented by The Secretary, Department of Health and Human Services Office of Technology Transfer National Institute of Health Papillomavirus pseudoviruses for detection and therapy of tumors
CN101918041A (zh) * 2007-10-12 2010-12-15 超分子有限公司 用于肿瘤诊断和治疗的氯毒素剂的系统性给药
US20110288234A1 (en) * 2008-02-19 2011-11-24 The Research Foundation on State University of NY Silica nanoparticles postloaded with photosensitizers for drug delivery in photodynamic therapy
EP2712627A3 (en) * 2008-02-27 2014-04-16 Yeda Research And Development Co. Ltd. RGD-(bacterio)chlorophyll conjugates for photodynamic therapy and imaging of necrotic tumors
EP2210590A1 (en) 2009-01-26 2010-07-28 Academisch Medisch Centrum Drug delivery system for use in the treatment of vascular and vessel-related pathologies
LT3964502T (lt) 2009-03-19 2024-08-26 The Johns Hopkins University Junginiai nukreipti į psma ir jų panaudojimas
WO2011008814A2 (en) 2009-07-14 2011-01-20 Immune Tolerance Institute, Inc., A California Not-For-Profit Corporation Multiplexed measurement of exogenous and endogenous dna
CA2768460A1 (en) 2009-07-16 2011-01-20 Glaxo Group Limited Antagonists, uses & methods for partially inhibiting tnfr1
US20120128670A1 (en) * 2009-07-31 2012-05-24 OSI Pharmaceuticals, LLC mTOR INHIBITOR AND ANGIOGENESIS INHIBITOR COMBINATION THERAPY
US20130224115A1 (en) * 2010-04-01 2013-08-29 Baylor College Of Medicine Non-radioactive agents for neuroblastoma imaging
CN103097403B (zh) 2010-05-11 2017-04-19 弗雷德哈钦森癌症研究中心 氯毒素变体、缀合物及其使用方法
WO2012024396A2 (en) 2010-08-17 2012-02-23 Rutgers, The State University Of New Jersey Compositions and methods for delivering nucleic acid molecules and treating cancer
US20130287688A1 (en) * 2010-11-18 2013-10-31 Xtuit Pharmaceuticals, Inc. Novel compositions and uses of anti-hypertension agents for cancer therapy
WO2012078877A2 (en) 2010-12-08 2012-06-14 Invicro, Llc Estimating pharmacokinetic parameters in imaging
CN102526055B (zh) * 2010-12-24 2014-01-01 北京工业大学 环乙二胺基竹红菌乙素在光动力抗肿瘤药物中的应用
US20130116408A1 (en) 2011-11-05 2013-05-09 Aura Biosciences, Inc. Virion Derived Protein Nanoparticles For Delivering Radioisotopes For The Diagnosis And Treatment Of Malignant And Systemic Disease And The Monitoring Of Therapy
GB201306627D0 (en) * 2013-04-11 2013-05-29 Thompson Richard Marker
EP3148583B1 (en) 2014-06-02 2020-04-29 Li-Cor, Inc. Phthalocyanine probes and uses thereof

Patent Citations (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020114793A1 (en) * 1999-04-20 2002-08-22 Edelson Richard Leslie Methods for inducing the differentiation of monocytes into functional dendritic cells and immunotherapeutic compositions including such dendritic cells
US20030139466A1 (en) * 2001-11-29 2003-07-24 Peritt David L. Methods for pretreating a subject with extracorporeal photopheresis
US20050112131A1 (en) * 2002-03-25 2005-05-26 Brian Pogue Methods of adjuvant photodynamic therapy to enhance radiation sensitization
US20060134001A1 (en) * 2002-07-12 2006-06-22 Frangioni John V Conjugated infrared fluorescent substances for detection of cell death
US20080193431A1 (en) * 2003-11-14 2008-08-14 University Of Pennsylvania Activatable photodynamic therapy agents
US8133482B2 (en) * 2003-11-14 2012-03-13 The Trustees Of The University Of Pennsylvania Activatable photodynamic therapy agents
US8889835B2 (en) * 2005-04-06 2014-11-18 Immunomedics, Inc. Polymeric carriers of therapeutic agents and recognition moieties for antibody-based targeting of disease sites
WO2007070680A2 (en) * 2005-12-16 2007-06-21 The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Optically detectable probes for identification and treatment of tumors
US20090156976A1 (en) * 2007-03-01 2009-06-18 Martin Korbling Devices and Methods for Extracorporeal Ablation of Circulating Cells
US20100216226A1 (en) * 2009-02-25 2010-08-26 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Device, system, and method for controllably reducing inflammatory mediators in a subject
US20120010558A1 (en) * 2010-07-09 2012-01-12 Services, National Institutes of Health Photosensitizing antibody-fluorophore conjugates
US20140120119A1 (en) * 2010-07-09 2014-05-01 The United States of America, as rep. by the Secretary, Dept. of Health and Human Services Photosensitizing antibody-fluorophore conjugates
US20130039860A1 (en) * 2010-10-20 2013-02-14 Li-Cor, Inc. Fluorescent imaging with substituted cyanine dyes
US20120228568A1 (en) * 2011-03-10 2012-09-13 Joseph Alfred Leon Nail/Bolt Slide Hammer Extractor
US20130131423A1 (en) * 2011-04-12 2013-05-23 Tianxin Wang Methods to detect and treat diseases
WO2013009475A9 (en) * 2011-07-11 2013-03-07 The United States Of America, As Represented By The Secretary, Department Of Health & Human Services Photosensitizing antibody-phuorophore conjugates
US20140161725A1 (en) * 2011-09-10 2014-06-12 Arizona Board Of Regents On Behalf Of The University Of Arizona Molecular Imaging of Cancer Cells In Vivo
US20160228568A1 (en) * 2013-09-18 2016-08-11 Aura Biosciences, Inc. Virus-like particle conjugates for diagnosis and treatment of tumors

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
"In Vivo Magnetic Enrichment Photoacoustic Diagnosis and Photothermal Purging of Infected Blood Using Multifunctional Gold and Magnetic Nanoparticles" Ekateriena GalahzhaEvegeny Shashkov,Justafa Sarimollaoglu,Karen Beenken,Alexei Basnakian,Mark Shirtliff,JonWoo Kim,Mark Smeltzer,Vladimir Zharov PLOS ONE September 2012 Vol 7 Issue 9 e45557 pp1-19 *

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11364297B2 (en) 2010-07-09 2022-06-21 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Photosensitizing antibody-fluorophore conjugates
US10538590B2 (en) 2010-07-09 2020-01-21 The United States Of America, As Represented By The Secretary, Dept. Of Health And Human Services Photosensitizing antibody-fluorophore conjugates
US10537641B2 (en) 2010-07-09 2020-01-21 The Usa As Represented By The Secretary, Department Of Health And Human Services Photosensitizing antibody-fluorophore conjugates
US11364298B2 (en) 2010-07-09 2022-06-21 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Photosensitizing antibody-fluorophore conjugates
US10588972B2 (en) 2014-06-02 2020-03-17 Li-Cor, Inc. Phthalocyanine probes and uses thereof
US10064943B2 (en) 2014-06-02 2018-09-04 Li-Cor, Inc. Therapeutic and diagnostic probes
US10830678B2 (en) 2014-08-08 2020-11-10 The United States Of America, As Represented By The Secretary, Department Of Health And Human Serv Photo-controlled removal of targets in vitro and in vivo
US11781955B2 (en) 2014-08-08 2023-10-10 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Photo-controlled removal of targets in vitro and in vivo
US11013803B2 (en) 2015-08-07 2021-05-25 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Near infrared photoimmunotherapy (NIR-PIT) of suppressor cells to treat cancer
US11141483B2 (en) 2015-08-18 2021-10-12 Rakuten Medical, Inc. Methods for manufacturing phthalocyanine dye conjugates and stable conjugates
US11147875B2 (en) 2015-08-18 2021-10-19 Rakuten Medical, Inc. Compositions, combinations and related methods for photoimmunotherapy
US11154620B2 (en) 2015-08-18 2021-10-26 Rakuten Medical, Inc. Compositions, combinations and related methods for photoimmunotherapy
US11827721B2 (en) 2018-03-02 2023-11-28 Universität Zürich and ETH Zurich Bioconjugates of antibodies and functionalized magnetic nanoparticles
US11678825B2 (en) * 2018-10-04 2023-06-20 Fenwal, Inc. Methods and systems for collecting samples in a photopheresis procedure

Also Published As

Publication number Publication date
US10588972B2 (en) 2020-03-17
EP3718570A1 (en) 2020-10-07
US20150374819A1 (en) 2015-12-31
CA2950299A1 (en) 2015-12-10
WO2015187677A1 (en) 2015-12-10
CN112999347A (zh) 2021-06-22
EP3148583B1 (en) 2020-04-29
WO2015187651A1 (en) 2015-12-10
US20200179514A1 (en) 2020-06-11
EP3148583A1 (en) 2017-04-05
JP2020125343A (ja) 2020-08-20
AU2015271830A1 (en) 2016-12-22
US10064943B2 (en) 2018-09-04
EP3148583A4 (en) 2018-01-17
JP2022023175A (ja) 2022-02-07
JP2017524659A (ja) 2017-08-31
US20180339048A1 (en) 2018-11-29
US20150343084A1 (en) 2015-12-03
CN106573054B (zh) 2021-04-13
JP6741599B2 (ja) 2020-08-19
CN106573054A (zh) 2017-04-19
AU2015271830B2 (en) 2020-03-05

Similar Documents

Publication Publication Date Title
US20150343060A1 (en) Treatment of circulating tumor cells using an extracorporeal device
Sato et al. Photoinduced ligand release from a silicon phthalocyanine dye conjugated with monoclonal antibodies: a mechanism of cancer cell cytotoxicity after near-infrared photoimmunotherapy
JP7425026B2 (ja) フタロシアニン色素コンジュゲートおよびその保存法
Fernandes et al. Photoimmunoconjugates: novel synthetic strategies to target and treat cancer by photodynamic therapy
JP2021105054A (ja) 光増感抗体−蛍光団コンジュゲート
US8057418B2 (en) Devices and methods for extracorporeal ablation of circulating cells
EP2784082B1 (en) Disease site-delivering pharmaceutical compositions comprising paclitaxel.
US11369425B2 (en) Lactoferrin-conjugated nanoparticle complex and use thereof
US20160058937A1 (en) Blood cleansing and apparatus & method
St Denis et al. Synthesis, bioanalysis and biodistribution of photosensitizer conjugates for photodynamic therapy
Kim et al. A novel therapeutic strategy of multimodal nanoconjugates for state-of-the-art brain tumor phototherapy
US20180169319A1 (en) Treatment of cancer by manipulating the immune system
Nishimura et al. Cancer neovasculature-targeted near-infrared photoimmunotherapy (NIR-PIT) for gastric cancer: different mechanisms of phototoxicity compared to cell membrane-targeted NIR-PIT
US20230226201A1 (en) Drug conjugate having enhanced drug delivery and internalization efficiency
Hirata et al. Near‐infrared photoimmunotherapy (NIR‐PIT) on cholangiocarcinoma using a novel catheter device with light emitting diodes
US20150122738A1 (en) Blood Cleansing System & Method
Hu et al. Albumin-Based Cyanine Crizotinib Conjugate Nanoparticles for NIR-II Imaging-Guided Synergistic Chemophototherapy
Peng et al. Photoimmunotherapy: a new paradigm in solid tumor immunotherapy
JP7216435B2 (ja) 血管を標的とする抗体と光増感剤とのコンジュゲート
US9808526B2 (en) Pharmaceutical kit and methods for cancer treatment via intracavity delivery and for preparing metal nanoparticle-antibody fragment conjugate
JP4696259B2 (ja) 新規光感受性薬剤及びその製造方法
Kobayashi Illuminating the cancer-targeting potential of near-infrared photoimmunotherapy
US20240100053A1 (en) Pharmaceutical composition
WO2024166416A1 (ja) 近赤外光線免疫療法の治療効果の評価方法
WO2022107573A1 (ja) 腫瘍微小環境をターゲットとする光免疫療法に用いる医薬組成物、治療効果確認のためのマーカー、及び検査方法

Legal Events

Date Code Title Description
AS Assignment

Owner name: LI-COR, INC., NEBRASKA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:KOVAR, JOY L.;WANG, HAN-WEI;SIGNING DATES FROM 20150616 TO 20150622;REEL/FRAME:035899/0663

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION

AS Assignment

Owner name: RAKUTEN MEDICAL, INC., CALIFORNIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:LI-COR, INC.;REEL/FRAME:055238/0885

Effective date: 20201230