The present disclosure arises at least in part from the seminal recognition that a combination treatment regimen including one or more cycles and/or doses of a checkpoint inhibitor and a therapeutic, either sequentially, in either order, or substantially simultaneously, can be more effective in treating cancer in some subjects and/or can initiate, enable, increase, enhance or prolong the activity and/or number of immune cells, or a medically beneficial response by a tumor.
A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps
A61F 7/00 - Appareils de chauffage ou de refroidissement pour traitement médical ou thérapeutique du corps humain
A61K 35/15 - Cellules de la lignée des myéloïdes, p. ex. granulocytes, basophiles, éosinophiles, neutrophiles, leucocytes, monocytes, macrophages ou mastocytesCellules précurseurs myéloïdesCellules présentatrices d’antigène, p. ex. cellules dendritiques
A61K 35/17 - LymphocytesLymphocytes BLymphocytes TCellules tueuses naturellesLymphocytes activés par un interféron ou une cytokine
A61K 39/39 - Préparations médicinales contenant des antigènes ou des anticorps caractérisées par les additifs immunostimulants, p. ex. par les adjuvants chimiques
A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
A61N 5/10 - RadiothérapieTraitement aux rayons gammaTraitement par irradiation de particules
C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
2.
COMBINATIONS OF CHECKPOINT INHIBITORS AND THERAPEUTICS TO TREAT CANCER
A combination treatment regimen including one or more cycles and/or doses of a checkpoint inhibitor and a therapeutic, either sequentially, in either order, or substantially simultaneously, can be more effective in treating cancer in some subjects and/or can initiate, enable, increase, enhance or prolong the activity and/or number of immune cells, the efficacy of anti-tumor immune responses or a medically beneficial response by a tumor.
A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps
A61F 7/00 - Appareils de chauffage ou de refroidissement pour traitement médical ou thérapeutique du corps humain
A61K 35/15 - Cellules de la lignée des myéloïdes, p. ex. granulocytes, basophiles, éosinophiles, neutrophiles, leucocytes, monocytes, macrophages ou mastocytesCellules précurseurs myéloïdesCellules présentatrices d’antigène, p. ex. cellules dendritiques
A61K 35/17 - LymphocytesLymphocytes BLymphocytes TCellules tueuses naturellesLymphocytes activés par un interféron ou une cytokine
A61K 39/39 - Préparations médicinales contenant des antigènes ou des anticorps caractérisées par les additifs immunostimulants, p. ex. par les adjuvants chimiques
A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
A61N 5/10 - RadiothérapieTraitement aux rayons gammaTraitement par irradiation de particules
C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
3.
IN VITRO METHODS AND COMPOSITIONS FOR ENHANCING THE ACTIVATION OF DENDRITIC CELLS AND T CELLS, AND FOR INDUCING A TH-1 IMMUNE RESPONSE
The present disclosure provides compositions and in vitro or ex vivo methods for obtaining an enhanced antigen specific Th1 immune response. The compositions can comprise activation enhanced dendritic cells or T cells produced in vitro. The methods comprise contacting immature dendritic cells with a maturation agent that comprises a dendritic cell maturation agent, interferon γ and an inflammation-activating lipid which can produced hyperactivated dendritic cells. The method can further comprise contacting the maturing dendritic cells with a predetermined antigen during maturation. An in vitro or ex vivo method is also provided wherein the hyperactive dendritic cells can be used to induce naive T cell activation, where the activated T cells can be formulated for administration to an individual in need of such treatment.
A61K 35/15 - Cellules de la lignée des myéloïdes, p. ex. granulocytes, basophiles, éosinophiles, neutrophiles, leucocytes, monocytes, macrophages ou mastocytesCellules précurseurs myéloïdesCellules présentatrices d’antigène, p. ex. cellules dendritiques
A61K 35/17 - LymphocytesLymphocytes BLymphocytes TCellules tueuses naturellesLymphocytes activés par un interféron ou une cytokine
A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
The present disclosure provides populations of cells comprising partially mature and optimally activated dendritic cells that can be used for administration to individuals having a cancer and/or tumor. Partially matured dendritic cells, those contacted with a dendritic cell maturation agent for about 10 to about 19 hours, upon administration efficiently take up and process tumor antigens in the area of the tumor site, complete maturation, and can subsequently migrate to the lymph nodes of a treated individual. Once in a lymph node the now fully mature antigen presenting dendritic cells secrete the appropriate cytokines (e.g., TNFα, IL-6, IL-8, and/or IL-12) and contact T cells inducing a substantial and optimal clinical and/or anti-tumor immune response.
A61K 35/15 - Cellules de la lignée des myéloïdes, p. ex. granulocytes, basophiles, éosinophiles, neutrophiles, leucocytes, monocytes, macrophages ou mastocytesCellules précurseurs myéloïdesCellules présentatrices d’antigène, p. ex. cellules dendritiques
A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps
The present disclosure provides compositions and in vitro or ex vivo methods for obtaining an enhanced antigen specific Th1 immune response. The compositions can comprise activation enhanced dendritic cells or T cells produced in vitro. The methods comprise contacting immature dendritic cells with a maturation agent that comprises a dendritic cell maturation agent, interferon ? and an inflammation-activating lipid which can produced hyperactivated dendritic cells. The method can further comprise contacting the maturing dendritic cells with a predetermined antigen during maturation. An in vitro or ex vivo method is also provided wherein the hyperactive dendritic cells can be used to induce naive T cell activation, where the activated T cells can be formulated for administration to an individual in need of such treatment.
in vitro ex vivoγ in vitrox vivox vivo method is also provided wherein the hyperactive dendritic cells can be used to induce naive T cell activation, where the activated T cells can be formulated for administration to an individual in need of such treatment.
The present disclosure provides partially mature and activated dendritic cells that produce levels of cytokines/chemokines, for example, one or any combination of and/or all of IL-6, IL-8, IL-12 and/or TNFα, that are correlated with improved clinical outcomes, significantly increased survival times and significantly increased times to tumor or cancer recurrence. The determined threshold amounts of these cytokines can be used for (i) a immunotherapeutic potency test for activated dendritic cells, (ii) selecting responder patients, (iii) rejecting non-responder patients, and (iv) to screen for dendritic cell activation or maturation agents that can also induce the production of the threshold amount of the cytokines/chemokines.
A61K 35/15 - Cellules de la lignée des myéloïdes, p. ex. granulocytes, basophiles, éosinophiles, neutrophiles, leucocytes, monocytes, macrophages ou mastocytesCellules précurseurs myéloïdesCellules présentatrices d’antigène, p. ex. cellules dendritiques
The present disclosure provides populations of cells comprising partially mature and optimally activated dendritic cells that can be used for administration to individuals having a cancer and/or tumor. Partially matured dendritic cells, those contacted with a dendritic cell maturation agent for about 10 to about 19 hours, upon administration efficiently take up and process tumor antigens in the area of the tumor site, complete maturation, and can subsequently migrate to the lymph nodes of a treated individual. Once in a lymph node the now fully mature antigen presenting dendritic cells secrete the appropriate cytokines (e.g., TNFa, IL-6, IL-8, and/or IL-12) and contact T cells inducing a substantial and optimal clinical and/or anti-tumor immune response.
A61K 35/15 - Cellules de la lignée des myéloïdes, p. ex. granulocytes, basophiles, éosinophiles, neutrophiles, leucocytes, monocytes, macrophages ou mastocytesCellules précurseurs myéloïdesCellules présentatrices d’antigène, p. ex. cellules dendritiques
A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps
The present disclosure provides partially mature and activated dendritic cells that produce levels of cytokines/chemokines, for example, one or any combination of, and/or all of IL-6, IL-8, IL-12 and/or TNFa, that are correlated with improved clinical outcomes, significantly increased survival times and significantly increased times to tumor or cancer recurrence. The determined threshold amounts of these cytokines can be used for (i) a immunotherapeutic potency test for activated dendritic cells, (ii) selecting responder patients, (iii) rejecting non-responder patients, and (iv) to screen for dendritic cell activation or maturation agents that can also induce the production of the threshold amount of the cytokines/chemokines.
The present disclosure provides partially mature and activated dendritic cells that produce levels of cytokines/chemokines, for example, one or any combination of, and/or all of IL-6, IL-8, IL-12 and/or TNFα, that are correlated with improved clinical outcomes, significantly increased survival times and significantly increased times to tumor or cancer recurrence. The determined threshold amounts of these cytokines can be used for (i) a immunotherapeutic potency test for activated dendritic cells, (ii) selecting responder patients, (iii) rejecting non-responder patients, and (iv) to screen for dendritic cell activation or maturation agents that can also induce the production of the threshold amount of the cytokines/chemokines.
A61K 35/15 - Cellules de la lignée des myéloïdes, p. ex. granulocytes, basophiles, éosinophiles, neutrophiles, leucocytes, monocytes, macrophages ou mastocytesCellules précurseurs myéloïdesCellules présentatrices d’antigène, p. ex. cellules dendritiques
11.
OPTIMALLY ACTIVATED DENDRITIC CELLS THAT INDUCE AN IMPROVED OR INCREASED ANTI-TUMOR IMMUNE RESPONSE
The present disclosure provides populations of cells comprising partially mature and optimally activated dendritic cells that can be used for administration to individuals having a cancer and/or tumor. Partially matured dendritic cells, those contacted with a dendritic cell maturation agent for about 10 to about 19 hours, upon administration efficiently take up and process tumor antigens in the area of the tumor site, complete maturation, and can subsequently migrate to the lymph nodes of a treated individual. Once in a lymph node the now fully mature antigen presenting dendritic cells secrete the appropriate cytokines (e.g., TNFa, IL-6, IL-8, and/or IL-12) and contact T cells inducing a substantial and optimal clinical and/or anti -tumor immune response.
The present disclosure provides populations of cells comprising partially mature and optimally activated dendritic cells that can be used for administration to individuals having a cancer and/or tumor. Partially matured dendritic cells, those contacted with a dendritic cell maturation agent for about 10 to about 19 hours, upon administration efficiently take up and process tumor antigens in the area of the tumor site, complete maturation, and can subsequently migrate to the lymph nodes of a treated individual. Once in a lymph node the now fully mature antigen presenting dendritic cells secrete the appropriate cytokines (e.g., TNFa, IL-6, IL-8, and/or IL-12) and contact T cells inducing a substantial and optimal clinical and/or anti -tumor immune response.
The present disclosure arises at least in part from the seminal recognition that a combination treatment regimen including one or more cycles and/or doses of a checkpoint inhibitor and a therapeutic, either sequentially, in either order, or substantially simultaneously, can be more effective in treating cancer in some subjects and/or can initiate, enable, increase, enhance or prolong the activity and/or number of immune cells, or a medically beneficial response by a tumor.
The present disclosure arises at least in part from the seminal recognition that a combination treatment regimen including one or more cycles and/or doses of a checkpoint inhibitor and a therapeutic, either sequentially, in either order, or substantially simultaneously, can be more effective in treating cancer in some subjects and/or can initiate, enable, increase, enhance or prolong the activity and/or number of immune cells, or a medically beneficial response by a tumor.
05 - Produits pharmaceutiques, vétérinaires et hygièniques
Produits et services
Immune cells, namely cells for medical or veterinary use; Biotechnology preparations for the prevention, management and treatment of cancer, or for the modulation of the immune system or particular elements of the immune system by increasing or decreasing the extent, timing or duration of the immune response or changing the nature of the immune response; Medical preparations for the prevention, management and treatment of cancer, or for the modulation of the immune system or particular elements of the immune system by increasing or decreasing the extent, timing or duration of the immune response or changing the nature of the immune response; Pharmaceutical preparations and substances for use as vaccine adjuvants, immune system stimulators or suppressors, and immune system modulators; Derivatives and modulators of immune cells, namely, vaccines, proteins, peptides, enzymes, cytokines, chemokines, antibodies, DNA, RNA, growth factors, cell lysate, extracellular matrix and conditioned media for medical or veterinary use; Vaccines
05 - Produits pharmaceutiques, vétérinaires et hygièniques
Produits et services
(1) Immune cells for medical and veterinary use namely biochemicals in the form of activated dendritic cells, antigens and monocyte white blood cells for the prevention, management and treatment of cancer, for the modulation of the immune system, and for the modulation of particular elements of the immune system by increasing and decreasing the extent, timing and duration of the immune response and changing the nature of the immune response; pharmaceutical preparations for the treatment of cancer; pharmaceutical preparations and substances for use as vaccine adjuvants, immune system stimulators and suppressors; derivatives and modulators of immune cells for medical and veterinary use namely biochemicals for the treatment of cancer namely proteins, peptides, enzymes, cytokines, chemokines, antibodies, DNA, RNA, growth factors, cell lysate, extracellular matrix and conditioned media; human and veterinary vaccines.
(2) Human vaccines.
05 - Produits pharmaceutiques, vétérinaires et hygièniques
Produits et services
Immune cells, namely cells for medical or veterinary use; Biotechnology preparations for the prevention, management and treatment of cancer, or for the modulation of the immune system or particular elements of the immune system by increasing or decreasing the extent, timing or duration of the immune response or changing the nature of the immune response; Medical preparations for the prevention, management and treatment of cancer, or for the modulation of the immune system or particular elements of the immune system by increasing or decreasing the extent, timing or duration of the immune response or changing the nature of the immune response; Pharmaceutical preparations and substances for use as vaccine adjuvants, immune system stimulators or suppressors, and immune system modulators; Derivatives and modulators of immune cells, namely, vaccines, proteins, peptides, enzymes, cytokines, chemokines, antibodies, DNA, RNA, growth factors, cell lysate, extracellular matrix and conditioned media for medical or veterinary use; Vaccines.
The present invention provides methods for inducing the maturation of immature dendritic cells (DC) and for activating those cells without the use of a dendritic cell maturation agent. The activated DC can be used for inducing an antigen specific T cell response. Methods of the invention can also comprise the addition of a directional maturation agent, such as interferon gamma, to induce a Th-1 and/or Th-2 bias in the response obtained. The present invention also provides dendritic cell populations useful for activating and for inducing antigen specific T cells. Similarly, activated antigen specific T cell populations, and methods of making the same are provided.
The present invention provides tangential flow filtration devices and methods for enriching a heterogenous mixture of blood constituents for leukocytes by removal of non-leukocyte blood constituents. In one particular embodiment the device can provide a composition enriched in monocytes.
C12Q 1/00 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions
B01D 21/00 - Séparation par sédimentation de particules solides en suspension dans des liquides
B01D 12/00 - Déplacement d'un liquide au moyen d'un autre liquide, p. ex. en retirant le liquide de solides humides, ou de dispersions de liquides, ou de solides se trouvant dans des liquides
The present invention provides methods for inducing the maturation of immature dendritic cells (DC) and for activating those cells without the use of a dendritic cell maturation agent. The activated DC can be used for inducing an antigen specific T cell response. Methods of the invention can also comprise the addition of a directional maturation agent, such as interferon gamma, to induce a Th-I and/or Th-2 bias in the response obtained. The present invention also provides dendritic cell populations useful for activating and for inducing antigen specific T cells. Similarly, activated antigen specific T cell populations, and methods of making the same are provided.
C12N 5/00 - Cellules non différenciées humaines, animales ou végétales, p. ex. lignées cellulairesTissusLeur culture ou conservationMilieux de culture à cet effet
The present invention provides methods for inducing the maturation of immature dendritic cells (DC) and for activating those cells without the use of a dendritic cell maturation agent. The activated DC can be used for inducing an antigen specific T cell response. Methods of the invention can also comprise the addition of a directional maturation agent, such as interferon gamma, to induce a Th-I and/or Th-2 bias in the response obtained. The present invention also provides dendritic cell populations useful for activating and for inducing antigen specific T cells. Similarly, activated antigen specific T cell populations, and methods of making the same are provided.
The present invention provides methods for enriching a heterogenous mixture of bone marrow or blood constituents for stem cells by removal of non-stem cell constituents comprising separation of the non-stem cell constituents using a tangential flow filtration device.
B01D 61/00 - Procédés de séparation utilisant des membranes semi-perméables, p. ex. dialyse, osmose ou ultrafiltrationAppareils, accessoires ou opérations auxiliaires, spécialement adaptés à cet effet
C12N 5/00 - Cellules non différenciées humaines, animales ou végétales, p. ex. lignées cellulairesTissusLeur culture ou conservationMilieux de culture à cet effet
The present invention provides tangential flow filtration devices and methods for enriching a heterogeneous mixture of blood constituents for leukocytes by removal of non-leukocyte blood constituents. In one particular embodiment the device can provide a composition enriched in monocytes. One embodiment includes a remover unit (1) having a crossflow chamber (3) separated by a microporous filter (5) from a filtrate chamber (4), the remover unit (1) also having a tangential flow inlet (6), a fluid outlet (7) for a fluid enriched in leukocytes and a filtrate outlet (8).
The present invention provides methods for enriching a heterogenous mixture of bone marrow or blood constituents for stem cells by removal of non-stem cell constituents comprising separation of the non-stem cell constituents using a tangential flow filtration device.
C12N 5/00 - Cellules non différenciées humaines, animales ou végétales, p. ex. lignées cellulairesTissusLeur culture ou conservationMilieux de culture à cet effet
27.
ADMINISTRATION OF DENDRITIC CELLS PARTIALLY MATURED IN VITRO FOR THE TREATMENT OF TUMORS
The present invention provides populations of cells comprising partially matured dendritic cells that can be used for administration individuals having a tumor. Partially matured dendritic cells, those contacted with a dendritic cell maturation agent for about 1 to about 10 hours, or more, efficiently take up and process tumor antigens in the area of the tumor site, complete maturation, and can subsequently migrate to the lymph nodes of a treated individual. Once in the lymph node the now fully mature antigen presenting dendritic cells secrete the appropriate cytokines (e.g., TNF.alpha. and IL-12) and contact T cells inducing a substantial anti-tumor immune response.
A61K 35/15 - Cellules de la lignée des myéloïdes, p. ex. granulocytes, basophiles, éosinophiles, neutrophiles, leucocytes, monocytes, macrophages ou mastocytesCellules précurseurs myéloïdesCellules présentatrices d’antigène, p. ex. cellules dendritiques
A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps
