Abstract: The present invention concerns an in vivo method for introducing a naked mRNA molecule into the cytosol of a cell(s) in a subject, by the use of photochemical internalization, wherein the photosensitising agent is a sulphonated meso-tetraphenyl chlorin, sulfonated tetraphenylporphine or a di- or tetrasulfonated aluminium phthalocyanine used in an amount of 0.000001-0.001 ?g and the cells(s) are contacted with the mRNA molecule and photosensitising agent for 30 seconds to 10 minutes before irradiation of the cell(s). The method may be used to express a polypeptide in the subject. The method is also directed to pharmaceutical compositions containing the photosensitising agents and the mRNA and uses of the molecules in therapy, e.g. to treat or prevent cancer or an infection.

Abstract: A method of treating or preventing an intracellular bacterial infection, comprising contacting the cell(s) which are infected with an antibacterial agent and a photosensitizing agent and irradiating the cell(s) with light of a wavelength effective to activate the photosensitizing agent, wherein the antibacterial agent is released into the cytosol of the cell(s) and kills, damages or prevents the replication of bacteria in said cell(s) is described. Related uses, and compositions, products and kits for the same are further described.

Abstract: The invention concerns a method of generating an immune response in a subject, comprising administering to the subject an antigenic molecule, a photosensitizing agent, a checkpoint inhibitor, and irradiating said subject with light of a wavelength effective to activate the photosensitizing agent to generate an immune response. Preferably the method is a method of vaccination. The invention also provides related methods, compositions, cells, uses, products and kits.

Abstract: The present invention relates to a method of treating or preventing melanoma using vaccination or immunisation, wherein said vaccination or immunisation involves the use of a photosensitizing agent, a melanoma antigen (i.e. an antigenic molecule), for example a vaccine component, and irradiation with light of a wavelength effective to activate the photosensitizing agent. The invention also relates to said photosensitizing agent and melanoma antigen for use in such a method, and to cells produced by the method.

Abstract: The present invention concerns an in vivo method for introducing an mRNA molecule (which is not associated with a carrier) into the cytosol of a cell(s) in a subject, by the use of photochemical internalization, wherein the photosensitising agent is a sulphonated meso-tetraphenyl chlorin, sulfonated tetraphenylporphine or a di- or tetrasulfonated aluminium phthalocyanine used in an amount of 0.0001 to 1 ?g. The method may be used to express a polypeptide in the subject. The invention is also directed to pharmaceutical compositions containing the photosensitising agents and the mRNA and uses of the molecules in therapy, e.g. to treat or prevent cancer or an infection.

Abstract: The present invention provides a method of treating a cholangiocarcinoma in a human patient comprising a photochemical internalization method using TPCS2a, and gemcitabine and optionally another cytotoxic agent, preferably cisplatin. Related uses and kit for performing the invention are also provided.

Abstract: The present invention provides a method of treating or preventing an intracellular bacterial infection, comprising contacting the cell(s) which are infected with an antibacterial agent and a photosensitizing agent and irradiating the cell(s) with light of a wavelength effective to activate the photosensitizing agent, wherein the antibacterial agent is released into the cytosol of the cell(s) and kills, damages or prevents the replication of bacteria in said cell(s). The invention also provides related uses, and compositions, products and kits for the same.

Abstract: A method of vaccination or immunisation involving the use of a photosensitizing agent, an antigenic molecule, e.g. a vaccine component, and an agent which enhances the effect of photochemical internalization (PCI)-mediated vaccination is disclosed wherein the agent is a ligand for a Toll-like receptor (TLR), and irradiation is with light of a wavelength effective to activate the photosensitizing agent. Antigenic, e.g. vaccine compositions, useful in such a method are also disclosed along with a method of generating antigen presenting cells which may be used to generate an immune response based on introducing antigenic molecules, e.g. vaccine components, into cells to achieve antigen presentation. The invention also provides methods of achieving vaccination in a subject using such cells.

Abstract: The present invention provides a method of expressing an antigenic molecule or a part thereof on the surface of a cell using a photochemical internalization method in which a cytokine, preferably GM-CSF, is used to enhance the method. The method may be used to stimulate an immune response and for various therapeutic or prophylactic methods. Pharmaceutical compositions or kits comprising the components for use in the method, cells produced by the method and their use in therapy and prophylaxis also form aspects of the invention.

Abstract: A device for activating light-induced rupture of endocytic vesicles in target cells of a patient so as to effect delivery of an administered antigen to cytosol in the target cells, is described. The device is adapted to be worn by a patient over a region of skin where an antigen and a photosensitising agent are to be administered. The device comprises a rear surface that is rounded or otherwise configured to be worn against the patient's skin. It has a retaining part for retaining the device in place over the region of the patient's skin during an activation cycle. A light source is arranged to illuminate the patient's skin from the rear of the device. A control system is configured to vary the output of the light source with respect to time in accordance with a pre-configured output sequence.

Abstract: The present invention relates to novel chitosan-based conjugates, e.g. nanocarriers, comprising a derivative of the biocompatible polymer chitosan conjugated to a photosensitizing agent, and uses thereof in photochemical internalization (PCI) and photodynamic therapy (PDT). The invention also relates to the use of the novel conjugates of the invention in treatment or prevention of diseases, particularly cancer, and for vaccination purposes.

Abstract: The invention concerns a method of generating an immune response in a subject, comprising administering to the subject an antigenic molecule, a photosensitizing agent, a checkpoint inhibitor, and irradiating said subject with light of a wavelength effective to activate the photosensitizing agent to generate an immune response. Preferably the method is a method of vaccination. The invention also provides related methods, compositions, cells, uses, products and kits.

Abstract: The present invention provides a method of expressing an antigenic molecule or a part thereof on the surface of a cell using a photochemical internalisation method in which a cytokine, preferably GM-CSF, is used to enhance the method. The method may be used to stimulate an immune response and for various therapeutic or prophylactic methods. Pharmaceutical compositions or kits comprising the components for use in the method, cells produced by the method and their use in therapy and prophylaxis also form aspects of the invention.

Abstract: The present invention provides a method of stimulating an immune response to an antigenic molecule, by contacting a cell with the antigenic molecule and with a photosensitizing agent, irradiating the cell, and thereby presenting the antigenic molecule, or part thereof, on the surface of said cell and stimulating an immune response.

Abstract: The present invention relates to a method for introducing an siRNA molecule into the cytosol of a cell, said method comprising i) contacting said cell with an siRNA molecule, a carrier and a photosensitizing agent, and ii) irradiating the cell with light of a wavelength effective to activate the photosensitizing agent, wherein said carrier comprises a cationic polyamine such as a lipopolyamine in a non-liposomal formulation, polyethyleneimine (PEI), a betacyclodextrin amine polymer, an amine group containing dendrimer, and a cationic peptide. Cells or a population of cells obtainable by the method, a composition containing an siRNA molecule and the carrier molecule, kits and therapeutic uses of the above are also provided.

Abstract: The present invention relates to a method of treating or preventing melanoma using vaccination or immunisation, wherein said vaccination or immunisation involves the use of a photosensitizing agent, a melanoma antigen (i.e. an antigenic molecule), for example a vaccine component, and irradiation with light of a wavelength effective to activate the photosensitizing agent. The invention also relates to said photosensitizing agent and melanoma antigen for use in such a method, and to cells produced by the method.

Abstract: A method of vaccination or immunisation involving the use of a photosensitizing agent, an antigenic molecule, e.g. a vaccine component, and an agent which enhances the effect of photochemical internalization (PCI)-mediated vaccination is disclosed wherein the agent is a ligand for a Toll-like receptor (TLR), and irradiation is with light of a wavelength effective to activate the photosensitizing agent. Antigenic, e.g. vaccine compositions, useful in such a method are also disclosed along with a method of generating antigen presenting cells which may be used to generate an immune response based on introducing antigenic molecules, e.g. vaccine components, into cells to achieve antigen presentation. The invention also provides methods of achieving vaccination in a subject using such cells.

Abstract: A device for activating light-induced rupture of endocytic vesicles in target cells of a patient so as to effect delivery of an administered antigen to cytosol in the target cells, is described. The device is adapted to be worn by a patient over a region of skin where an antigen and a photosensitising agent are to be administered. The device comprises a rear surface that is rounded or otherwise configured to be worn against the patient's skin. It has a retaining part for retaining the device in place over the region of the patient's skin during an activation cycle. A light source is arranged to illuminate the patient's skin from the rear of the device. A control system is configured to vary the output of the light source with respect to time in accordance with a pre-configured output sequence.

Abstract: The present invention provides an in vitro method of expressing an antigenic molecule or a part thereof on the surface of a dendritic cell using a PCI method with TPCS2a at a concentration of 0.020-0.1 ?g/ml, using light of a wavelength of between 400 and 500 nm. Methods of treatment such as vaccination comprising this method, together with compositions comprising said cells and uses involving said cells expressing antigenic molecules are also provided.

Abstract: The present invention relates to a method for enhancing the activity of kinase inhibitors in target cells, and more specifically for enhancing the activity of tyrosine kinase inhibitors (TKIs), said method comprising contacting a cell with a kinase inhibitor and a photosensitizing agent and irradiating said cell with light of a wavelength effective to activate the photosensitizing agent, and to the use of this method for enhancing the effects of kinase inhibitors or kinase inhibitor-based drugs in particular to achieve cell death, for example, in cancer treatment and other diseases or conditions in which kinase inhibitors, such as TKIs, have a beneficial effect.