Immunotherapy involving CD28 stimulation
AssigneeThe Regents of the University of Michigan
InventorsCraig B. Thompson, Carl H. June, Jeffrey A. Ledbetter, Tullia Lindsten
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Abstract
A method of immunotherapy stimulates the T cell CD28 surface molecule to enhance T cell proliferation and increase overall lymphokine levels or to increase cellular production of human TH1 lymphokines or both. The method is selective for the induction of activated T cell mediated immune responses and enhances immune function even in the presence of immunosuppresants.
Claims32
A method of immunotherapy comprising the step of:
- selectively regulating the in vivo level of a human T-cell lymphokine by administering a therapeutically effective amount of a ligand to a patient having a population of activated T cells, said ligand having binding specificity for at least a portion of the extracellular domain of CD28.
A method of immunotherapy for selectively enhancing a T cell-mediated immune response specific for an antigen to which the recipient of said immunotherapy is sensitized by in vivo exposure thereto, said recipient thereby having a population of T cells undergoing activation, said method comprising the steps of:
- a) selecting a CD28 stimulator capable of binding to the extracellular domain of the CD28 molecule;
- b) providing said stimulator in a biologically compatible form suitable for administration in vivo;
- and
- c) administering said stimulator in said biologically compatible form in an amount sufficient for and for a time sufficient for said stimulator to bind to at least a portion of said population of T cells undergoing activation.
A method of augmenting a T-cell mediated immune response in an immunosuppressed patient comprising the steps of:
- a) providing an anti-CD28 antibody, said antibody having the characteristic of inducing the in vitro proliferation of cyclosporine-treated T cells when said antibody is used in conjunction with PMA;
- b) providing at least a portion of said anti-CD28 antibody in a biologically compatible form suitable for administration in vivo;
- and
- c) administering said portion of said anti-CD28 antibody in said biologically compatible form to said immunodepressed patient in a therapeutically effective amount, said amount being sufficient to enhance a T cell-mediated immune response.
A method for substantially increasing the cellular production of selected T cell lymphokines by a population of human T cells comprising the steps of:
- a) providing an in vivo population of T cells undergoing activation, wherein said T cells are activated by the binding of a first ligand to a stimulatory site of the surface of said T cell to stimulate said site, wherein said stimulation of at least a portion of said population is maximized, and
- b) stimulating the CD28 T cell surface molecule by binding said molecule with a second ligand having binding specificity for the extracellular domain of said CD28 molecule.
Dependencies are inferred from the claim text.