Peptoid ligands for isolation and treatment of autoimmune t-cells
AssigneeBoard of Regents, The University of Texas System
InventorsAnne R. Gocke, D. Gomika Udugamasooriya, Thomas Kodadek
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Abstract
The present invention provides for the identification of autoreactive T cell populations from individuals having autoimmune diseases, such as multiple sclerosis and EAE. Peptoids recognized by autoreactive T cells can be used to identify various types of autoimmune disease, and can also be used to target therapies against such populations.
Claims63
A method of identifying a ligand that is specifically recognized by autoimmune T cells comprising:
- (a) providing a first T cell population from a healthy subject, wherein said population is labeled with a first detectable label;
- (b) providing a second T cell population from a subject having an autoimmune disease, wherein said population is labeled with a second detectable label;
- (c) contacting said first and second T cell populations with a plurality of candidate ligands;
- and
- (d) assessing binding of said first and second T cell populations to said candidate ligands,
- wherein if said ligand binds to said second T cell population but not to said first T cell population, the said ligand is recognized by autoimmune but not healthy T cells.
A method of removing an autoimmune T cell from a subject suffering from an autoimmune disease comprising:
- (a) providing a ligand that binds specifically to autoimmune T cells, wherein said ligand is bound to a support;
- (b) contacting a T cell-containing sample from said subject with said support-bound ligand for a sufficient time to permit binding of autoimmune T cells to said support-bound ligand;
- and
- (c) separating said support from said sample.
The method of claim 11, wherein the ligand is a peptoid as described in claims 44-63.
A method of killing an autoimmune T cell obtained from a subject suffering from an autoimmune disease comprising:
- (a) providing a ligand that binds specifically to autoimmune T cells, wherein said ligand is conjugated to a toxin;
- and
- (b) contacting a T cell-containing sample from said subject with said conjugate for a sufficient time to permit binding of at least one autoimmune T cell to said conjugate,
- wherein said conjugate causes death of said autoimmune T cell.
The method of claim 22, wherein the ligand is a peptoid as described in claims 44-63.
A method of killing an autoimmune T cell obtained from or in a subject suffering from an autoimmune disease comprising:
- (a) providing a ligand that binds specifically to autoimmune T cells, wherein said ligand is conjugated to an IgG Fc-containing molecule;
- and
- (b) contacting an autoimmune T cell population with said conjugate for a sufficient time to permit binding of at least one autoimmune T cell to said conjugate,
- wherein said conjugate recruits immune effectors to said autoimmune T cells resulting in death thereof.
The method of claim 33, wherein the ligand is a peptoid as described in claims 44-63.
A peptoid having the formula:
- wherein n is 0-8;
- L is linker;
- Y is toxin or antibody fragments;
- and R1, R2, R3, R4, R5, R6, R7, R8 (with each value of n above 4 adding a next R group in numerical order to Formula I or Formula II), can be hydrogen;
- alkyl;
- allyl;
- methyl;
- ethyl;
- n-propyl;
- isopropyl;
- n-butyl;
- isobutyl;
- sec-butyl;
- tert-butyl;
- pentyl;
- hexyl;
- isopentyl;
- aryl;
- heteroaryl;
- furanyl;
- indolyl;
- thiophenyl;
- thiazolyl;
- imidazolyl;
- isoxazoyl;
- oxazoyl;
- piperonyl;
- pyrazoyl;
- pyrrolyl;
- pyrazinyl;
- pyridyl;
- pyrimidyl;
- pyrimidinyl;
- purinyl;
- cinnolinyl;
- benzofuranyl;
- benzothienyl;
- benzotriazolyl;
- benzoxazolyl;
- quinoline;
- isoxazolyl;
- isoquinoline cycloalkyl;
- alkenyl;
- cycloalkenyl;
- phenyl;
- pyridyl;
- methoxyethyl;
- (R)-methylbenzyl;
- C1-C6 alkyl unsubstituted or substituted with NH2, OH, SH, N(C1-C6 alkyl)2, O(C1-C6 alkyl), or S(C1-C6 alkyl);
- C2-C6 alkynyl unsubstituted or substituted with NH2, OH, SH, N(C1-C6 alkyl)2, O(C1-C6 alkyl), or S(C1-C6 alkyl);
- C2-C6 alkenyl unsubstituted or substituted with NH2, OH, SH, N(C1-C6 alkyl)2, O(C1-C6 alkyl), or S(C1-C6 alkyl).
Dependencies are inferred from the claim text.