摘要:
This invention provides methods to prepare and use immunostimulatory cells for enhancing an immune response. The invention provides a method for preparing mature dendritic cells (DCs), comprising the sequential steps of: (a) signaling isolated immature dendritic cells (iDCs) with a first signal comprising an interferon gamma receptor (IFN-³R) agonist and/or a tumor necrosis factor alpha receptor (TNF-±R) agonist to produce signaled dendritic cells; and (b) signaling said signaled dendritic cells with a second transient signal comprising an effective amount of a CD40 agonist to produce CCR7+ mature dendritic cells. Also provided by this invention are enriched populations of dendritic cells prepared by the methods of the invention. Such dendritic cells have enhanced immunostimulatory properties and increased IL-12 secretion and/or decreased IL-10 secretion. CD40 signaling can be initiated by one or more of polypeptide translated from an exogenous polynucleotide encoding CD40L (e.g. mRNA or DNA), an agonistic antibody to CD40 receptor or by CD40 ligand polypeptide. The enriched populations can be further modified by the administration of an immunogen to the DC. The DC will take up and process the immunogen on its cell surface.
摘要:
A one-step method for producing antigen loaded antigen-presenting cells from monocytes ex vivo has been found which comprises contacting the monocytes with a composition comprising an activator such as TNF alpha preferably in combination with at least one growth factor such as GM-CSF and at least one soluble or particulate antigen. According to the methods of the present invention, antigen-loaded dendritic cell vaccines can be generated within as little as three (3) days. In another method of the present invention, antigen loaded antigen-presenting cells are produced from monocytes ex vivo by contacting the monocytes with TNF alpha and granulocyte-macrophage colony stimulating factor at one time point to form antigen-presenting cells and then contacting antigenpresenting cells with soluble or particulate antigenic material at a second time point to form antigen loaded antigen-presenting cells, wherein the antigen loaded antigen-presenting cells are produced in less than four days. The present invention also includes a vaccine which comprises monocyte-derived antigen loaded antigen-presenting cells, wherein the antigenpresenting cells are composed of two or more subsets selected from the group consisting of Langerhans cells with surface markers (CD 1 a+ CD207+); interstitial dendritic cells with surface markers (CD 1a+ CD207-); double negative dendritic cells with surface markers 20 (CD 1 a-CD 14-); and dendritic cells with surface markers (CD 14+ CD 1 a- CD209+).
摘要:
A composition for inducing an immune response in a mammal, comprises lymphoid cells in which expression of tumor antigens has been chemically induced. The tumor antigens are induced in proliferating normal lymphoid cells, especially during the log phase of proliferation. The proliferation of the normal lymphoid cells is stimulated by normal mature dendritic cells. Most conveniently, the lymphoid cells are lymphocytes, especially peripheral blood lymphocytes. The tumor antigens are typically cancer/testis antigens, which may be chemically induced by DNA demethylation. Cancer/testis antigens are expressed in a wide range of tumors, so the composition is able to raise an immune response that is effective against a wide range of tumors, despite the fact that it is derived from normal cells. The composition may be used for preparation of an anti-tumor vaccine for prophylactic or therapeutic use. The composition may also be used for ex vivo activation of cytotoxic T lymphocytes, followed by expansion of the cytotoxic T lymphocyte population by normal dendritic cells, for cancer treatment by adoptive T cell immunotherapy.
摘要:
The present invention relates to compositions and methods for producing antigen-presenting cells, in vitro, ex vivo or in vivo. This invention relates more particularly to methods and compositions for producing dendritic cells using interleukin-15, preferably in combination with a growth factor such as GM-CSF. This invention is particularly suited for producing immature dendritic cells and activated cells from precursors, in vitro, ex vivo or in vivo. The invention also relates to compositions for implementing these methods, as well as compositions comprising antigen-presenting cells and uses thereof. Dendritic cells or membrane vesicles derived thereforom have utility in many applications, including diagnostic, therapy, vaccination, research, screening and gene delivery.
摘要:
This invention provides methods to prepare and use immunostimulatory cells for enhancing an immune response. The invention provides a method for preparing mature dendritic cells (DCs), comprising the sequential steps of: (a) signaling isolated immature dendritic cells (iDCs) with a first signal comprising an interferon gamma receptor (IFN-³R) agonist and/or a tumor necrosis factor alpha receptor (TNF-±R) agonist to produce signaled dendritic cells; and (b) signaling said signaled dendritic cells with a second transient signal comprising an effective amount of a CD40 agonist to produce CCR7+ mature dendritic cells. Also provided by this invention are enriched populations of dendritic cells prepared by the methods of the invention. Such dendritic cells have enhanced immunostimulatory properties and increased IL-12 secretion and/or decreased IL-10 secretion. CD40 signaling can be initiated by one or more of polypeptide translated from an exogenous polynucleotide encoding CD40L (e.g. mRNA or DNA), an agonistic antibody to CD40 receptor or by CD40 ligand polypeptide. The enriched populations can be further modified by the administration of an immunogen to the DC. The DC will take up and process the immunogen on its cell surface.
摘要:
This invention provides the field of therapeutics. Most specifically present invention provides methods of generating in vitro engineered dendritic cells conditionally expressing interleukin-12 (IL- 12) under the control of a gene expression modulation system in the presence of activating ligand and uses for therapeutic purposes in animals including human.
摘要:
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., TNFα and IL-12) and contact T cells inducing a substantial anti-tumor immune response.
摘要:
The present invention relates to regulation of antigen presentation by cytokine signaling regulators in antigen presenting cells, such as dendritic cells. The invention provides methods of modulating antigen presentation through modulation of cytokine signaling regulators, such as SOCS (SOCS1-7, CIS), SHP (SHP-1 and SHP-2) or PIAS (PIAS1, PIAS3, PIASx and PIASy). The present invention provides vaccines and therapies in which antigen presentation is enhanced through modulation of cytokine signaling regulators. The present invention also provides a mechanism to break self tolerance in tumor vaccination methods that rely on presentation of self tumor antigens.