TCR mimic antibodies as vascular targeting tools
The present invention includes a method of delivering a therapeutic agent into and across an endothelial cell (EC) in a subject in need thereof, comprising: attaching to a T Cell receptor mimic (TCR mimic) an active agent to form a therapeutic agent; and administering to the subject the therapeutic agent in a pharmaceutically acceptable carrier, wherein the therapeutic agent effectively crosses the EC microvascular barrier. Furthermore, the present invention relates to methods of treating diseases (particularly neuronal diseases) or conditions comprising identifying a subject in need of such a treatment and administering to said subject a composition comprising a TCR mimic conjugated to an active agent.
1. A method of delivering a therapeutic agent into and across an endothelial cell (EC) in a subject in need thereof, comprising:
attaching to a TCR mimic an active agent to form a therapeutic agent, wherein the TCR mimic is capable of binding a human HLA-A2 cell surface protein and crossing a brain EC microvascular barrier into the brain; and
administering to the subject the therapeutic agent in a pharmaceutically acceptable carrier, wherein the therapeutic agent effectively crosses the brain EC microvascular barrier into the brain.
2. The method of claim 1 , wherein the barrier being crossed is the blood-brain barrier (BBB), in a subject with (i) a CNS disease or disorder or (ii) a peripheral disease or disorder with CNS involvement.
3. The method of claim 2 , wherein the disease or disorder is a brain tumor.
4. The method of claim 1 , wherein the therapeutic agent or carrier is directly conjugated to a targeting molecule by covalent bonding which conjugation is optionally effected via a spacer or linker that bridges between the therapeutic agent or carrier and the targeting molecule.
5. The method of claim 4 , wherein the therapeutic agent-targeting molecule conjugate or carrier-targeting molecule conjugate is a recombinant fusion polypeptide.
6. The method of claim 1 , wherein the active agent is an antineoplastic agent.
7. The method of claim 1 , wherein the subject has or is suspected of a metabolic disorder.
8. A method for treating a neuronal disease or condition comprising:
identifying a subject in need of such treatment for the neuronal disease or condition;
administering to the subject in need of such treatment a neuroprotective and/or neurorestorative agent in an amount effective to treat the disorder in the subject, wherein the agent comprises:
a TCR mimic that targets an MHC-peptide combination, wherein the MHC is a human HLA-A2 protein found on the surface of an endothelial cells of the neuronal vasculature that is conjugated to an active agent to form a therapeutic agent, wherein the TCR mimic is capable of crossing a brain EC microvascular barrier into the brain.
9. The method of claim 8 , wherein the disease or disorder is a brain tumor.
10. The method of claim 8 , wherein the therapeutic agent or carrier is directly conjugated to a targeting molecule by covalent bonding; which conjugation is optionally effected via a spacer or linker that bridges between the therapeutic agent or carrier and the targeting molecule.
11. The method of claim 10 , wherein the therapeutic agent-targeting molecule conjugate or carrier-targeting molecule conjugate is a recombinant fusion polypeptide.
12. The method of claim 8 , wherein the step of administering intravenously.
13. The method of claim 8 , wherein the subject has or is suspected of having a metabolic disorder.
14. The method of claim 8 , wherein the active agent is an antineoplastic agent.
15. A method for treating a disease or condition in which a therapeutic agent has to cross an epithelial layer of a vasculature comprising:
identifying a subject in need of such treatment for the disease or condition;
administering to the subject in need of such treatment the therapeutic agent in an amount effective to treat the disorder in the subject, wherein the agent comprises:
a TCR mimic that targets an MHC-peptide combination, wherein the MHC is a human HLA-A2 protein found on the surface of an endothelial cells that is conjugated to an active agent to form a therapeutic agent, wherein the TCR mimic is selected to cross a brain EC microvascular barrier into the brain.
16. The method of claim 15 , wherein the active agent is an antineoplastic agent.
17. The method of claim 15 , wherein the TCR mimic is RL6.
18. A method of delivering a therapeutic agent into and across an endothelial cell (EC) in a subject in need thereof, comprising:
attaching to a TCR mimic an active agent to form a therapeutic agent, wherein the TCR mimic is RL6, wherein the TCRm and is capable of crossing a brain EC microvascular barrier into the brain; and
administering to the subject the therapeutic agent in a pharmaceutically acceptable carrier, wherein the therapeutic agent effectively crosses the brain EC microvascular barrier into the brain.
19. The method of claim 18 , wherein the barrier being crossed is the blood-brain barrier (BBB), in a subject with (i) a CNS disease or disorder or (ii) a peripheral disease or disorder with CNS involvement.
20. The method of claim 18 , wherein the therapeutic agent or carrier is directly conjugated to a targeting molecule by covalent bonding which conjugation is optionally effected via a spacer or linker that bridges between the therapeutic agent or carrier and the targeting molecule.
21. The method of claim 18 , wherein the active agent is an antineoplastic agent.