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OwnerAndrew L. Mellor, David H. Munninventors
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The present invention is based on the discovery antigen-presenting cells (APCs) may be generated to have predetermined levels of expression of the intracellular enzyme, indoleamine 2,3-dioxygenase (IDO). Because expression of high levels of IDO is correlated with a reduced ability to stimulate T cell responses and an enhanced ability to induce immunologic tolerance, APCs having high levels of IDO may be used to increase tolerance in the immune system, as for example in transplant therapy or treatment of autoimmune disorders. For example, APCs having high levels of IDO, and expressing or loaded with at least one antigen from a donor tissue may be used to increase tolerance of the recipient to the donor's tissue. Alternatively, APCs having reduced levels of IDO expression and expressing or loaded with at least one antigen from a cancer or infectious pathogen may be used as vaccines to promote T cell responses and increase immunity.
A method of making antigen-presenting cells (APCs) for enhancing T-cell tolerance comprising the steps of:
A method for enhancing the number of tolerance-inducing antigen-presenting cells (APCs) in a subject comprising treating said subject to increase the production of APCs or their precursors (APC progenitors) expressing levels of indoleamine 2,3-dioxygenase (IDO) enzyme activity sufficient to suppress proliferation of T cells (IDO+ APCs).
A method for enhancing tolerance in a subject comprising the steps of:
A composition for enhancing T cell tolerance comprising isolated antigen-presenting cells (APCs) selected as comprising APCs expressing levels of indoleamine 2,3-dioxygenase (IDO) enzyme activity sufficient to suppress proliferation of T cells (IDO+ APCs).
An antigen-presenting cell selected as comprising expression of indoleamine 2,3-dioxygenase (IDO) enzyme activity at a level sufficient to suppress proliferation of T cells.
A method of making antigen-presenting cells (APCs) for enhancing T-cell dependent immunologic activation in a subject comprising the steps of:
A method for increasing the number of non-suppressive antigen-presenting cells (APCs) in a subject comprising treating said subject to increase the population of APCs or their precursors (APC progenitors) expressing levels of indoleamine 2,3-dioxygenase (IDO) enzyme activity not sufficient to cause suppression of T cell proliferation (IDOLO APCs).
A method for increasing the protective immune response in a subject comprising the steps of:
A composition for increasing T cell activation comprising isolated antigen-presenting cells (APCs) selected as comprising APCs expressing levels of indoleamine 2,3-dioxygenase (IDO) enzyme activity not sufficient to cause suppression of T cell proliferation (IDOLO APCs).
An isolated antigen-presenting cell (APC) selected as comprising levels of indoleamine 2,3-dioxygenase (IDO) enzyme activity not sufficient to cause suppression of T cell proliferation (IDOLO).
A method to determine the number of tolerance-inducing antigen-presenting cells (APCs) in a cell population comprising measuring the number of APCs expressing levels of indoleamine 2,3-dioxygenase (IDO) enzyme sufficient to suppress proliferation of T cells (IDO+ APCs) in said population.
A kit for determining the number of tolerance-inducing antigen-presenting cells (IDO+ APCs) in a cell population comprising reagents to measure levels of indoleamine 2,3-dioxygenase (IDO) enzyme in a population of APCs, wherein said reagents are packaged in at least one individual container.
A method quantify the ability of a population of antigen-presenting cells to suppress T cell proliferation comprising measuring the ability of said cell population to increase T cell proliferation in the presence of an IDO inhibitor as compared to in the absence of an IDO inhibitor.
A kit for determining the ability of a population of antigen-presenting cells to suppress T cell proliferation comprising an IDO inhibitor packaged in at least one individual container.
A method for assessing the relative risk of tumor progression in a subject comprising the steps of:
A method for assessing the risk of tumor progression in a subject comprising the steps of:
A kit for assessing the relative risk of tumor progression in a subject comprising reagents for detection of the enzyme indoleamine 2,3-dioxygenase (IDO) in a sample of tissue from a tumor or tumor draining lymph node from a subject, wherein said reagents are packaged in at least one individual container.
A kit for assessing the relative risk of tumor progression in a subject comprising reagents for detection of relative levels of expression of mip-3α in a sample of tissue from a tumor or tumor draining lymph node from a subject, wherein said reagents are packaged in at least one individual container.
Dependencies are inferred from the claim text.