Vascular targets for detecting, imaging and treating neoplasia or neovasculature

Abstract

Methods of delivering an agent in a tissue-specific manner, by targeting annexin A1, a derivative of annexin A1, or a binding partner of annexin A1, are described. The methods can be used for detecting, imaging and/or treating neoplasia, angiogenesis or neovasculature, as well as for diagnostics and methods of assessing treatment efficacy. Antibodies to annexin A1 are also described, as are methods screening for agents altering annexin A1 activity.

1 . A method of delivering an agent to, into and/or across vascular endothelium in a neoplasm-specific manner, comprising contacting the luminal endothelial surface and/or caveolae of vasculature with an agent selected from the group consisting of: an agent that specifically binds to annexin A1; an agent that specifically binds to a derivative of annexin A1; an agent that specifically binds to a specific binding partner of annexin A1 ; an agent that specifically binds to a specific binding partner of a derivative of annexin A1; annexin A1; and a derivative of annexin A1.  
   
   
       2 . A method of treating a neoplasm in an individual, comprising administering to the individual an annexin A1 therapeutic agent.  
   
   
       3 . The method of  claim 2 , wherein the annexin A1 therapeutic agent is an antibody to annexin A1 or to a derivative of annexin A1.  
   
   
       4 . The method of  claim 2 , wherein the annexin A1 therapeutic agent is annexin A1 or a derivative of annexin A1.  
   
   
       5 . The method of  claim 2 , wherein the annexin A1 therapeutic agent is an annexin A1 receptor or an annexin A1 binding partner.  
   
   
       6 . The method of  claim 2 , wherein the annexin A1 therapeutic agent is an agent that comprises an active agent component and a targeting agent component, wherein the active agent component is selected from the group consisting of: a radionuclide; a chemotherapeutic agent; an immune stimulatory agent; an anti-neoplastic agent: an anti-inflammatory agent; a pro-inflammatory agent; a pro-apoptotic agent; a pro-coagulant; a toxin; an antibiotic; a hormone; an enzyme; a protein (e.g., a recombinant protein or a recombinant modified protein); a carrier protein (e.g., albumin, modified albumin); a lytic agent; a small molecule; aptamers; cells, including modified cells; vaccine-induced or other immune cells; nanoparticles (e.g., albumin-based nanoparticles); transferrins; immunoglobulins; multivalent antibodies; lipids; lipoproteins; liposomes; an altered natural ligand; a gene or nucleic acid; RNA; siRNA; a viral or non-viral gene delivery vector; a prodrug; and a promolecule.  
   
   
       7 . The method of  claim 6 , wherein the targeting agent component is an agent that specifically binds to annexin A1 or to a derivative of annexin A1.  
   
   
       8 . The method of  claim 7 , wherein the targeting agent component is an antibody to annexin A1 or to a derivative of annexin A1.  
   
   
       9 . The method of  claim 6 , wherein the targeting agent component is annexin A1 or a derivative of annexin A1.  
   
   
       10 . The method of  claim 6 , wherein the targeting agent component is a specific binding partner of annexin A1 or a specific binding partner of a derivative of annexin A1.  
   
   
       11 . The method of  claim 6 , wherein the targeting agent component is an agent that binds to a specific binding partner of annexin A1 or to a specific binding partner of a derivative of annexin A1.  
   
   
       12 . A physiological composition comprising an annexin A1 therapeutic agent.  
   
   
       13 . A method of performing physical imaging of an individual, comprising administering to the individual an imaging agent comprising a targeting agent component and an imaging agent component, wherein the targeting agent component specifically binds to annexin A1 or to a derivative of annexin A1.  
   
   
       14 . The method of  claim 13 , wherein the targeting agent component is an antibody to annexin A1 or to a derivative of annexin A1.  
   
   
       15 . The method of  claim 13 , wherein the imaging agent component is selected from the group consisting of: a radioactive agent, radioisotope or radiopharmaceutical; a contrast agent; a magnetic agent or a paramagnetic agent; liposomes; ultrasound agents; nanoparticles; a gene vector or virus inducing a detecting agent; an enzyme; a prosthetic group; a fluorescent material; a luminescent material; and a bioluminescent material.  
   
   
       16 . A method of performing physical imaging of an individual, comprising administering to the individual an imaging agent comprising a targeting agent component and an imaging agent component, wherein the targeting agent component binds to a specific binding partner of annexin A1 or to a specific binding partner of a derivative of annexin A1.  
   
   
       17 . The method of  claim 16 , wherein the imaging agent component is selected from the group consisting of: a radioactive agent, radioisotope or radiopharmaceutical; a contrast agent; a magnetic agent or a paramagnetic agent; liposomes; ultrasound agents; nanoparticles; a gene vector or virus inducing a detecting agent; an enzyme; a prosthetic group; a fluorescent material; a luminescent material; and a bioluminescent material.  
   
   
       18 . A method of performing physical imaging of an individual, comprising administering to the individual an imaging agent comprising a targeting agent component and an imaging agent component, wherein the targeting agent component is selected from the group consisting of: annexin A1, a derivative of annexin A1, a specific binding partner of annexin A1, and a specific binding partner of a derivative of annexin A1.  
   
   
       19 . The method of  claim 18 , wherein the imaging agent component is selected from the group consisting of: a radioactive agent, radioisotope or radiopharmaceutical; a contrast agent; a magnetic agent or a paramagnetic agent; liposomes; ultrasound agents; nanoparticles; a gene vector or virus inducing a detecting agent; an enzyme; a prosthetic group; a fluorescent material; a luminescent material; and a bioluminescent material.  
   
   
       20 . A method of assessing an individual for the presence or absence of a neoplasm, comprising: 
 a) administering to the individual an agent of interest that comprises an imaging agent component and a targeting agent component, wherein the targeting agent component specifically binds to annexin A1 or a derivative of annexin A1, and    b) assessing the individual for the presence or absence of a concentration of the agent of interest,    wherein the presence of a concentration of the agent of interest is indicative of the presence of a neoplasm.    
   
   
       21 . The method of  claim 20 , wherein the targeting agent component is selected from the group consisting of: annexin A1; derivative of annexin A1; antibody to annexin A1 ; and a derivative of annexin A1.  
   
   
       22 . A method of assessing an individual for the presence or absence of a neoplasm, comprising: 
 a) administering to the individual an agent of interest that comprises an imaging agent component and a targeting agent component, wherein the targeting agent component binds to a specific binding partner of annexin A1 or to a specific binding partner of a derivative of annexin A1, and    b) assessing the individual for the presence or absence of a concentration of the agent of interest,    wherein the presence of a concentration of the agent of interest is indicative of the presence of a neoplasm.    
   
   
       23 . A method of assessing an individual for the presence or absence of a neoplasm, comprising: 
 a) administering to the individual an agent of interest that comprises an imaging agent component and a targeting agent component, wherein the targeting agent component is selected from the group consisting of: : annexin A1, a derivative of annexin A1, a binding partner of annexin A1, and a binding partner of a derivative of annexin A1; and    b) assessing the individual for the presence or absence of a concentration of the agent of interest,    wherein the presence of a concentration of the agent of interest is indicative of the presence of a neoplasm.    
   
   
       24 . A method of assessing an individual for the presence or absence of a neoplasm, comprising: 
 a) administering to the individual an agent of interest that comprises an imaging agent component and a targeting agent component, wherein the targeting agent component binds to a specific binding partner of annexin A1 or to a specific binding partner of a derivative of annexin A1;    b) taking a biopsy sample from the individual;    c) assessing the biopsy sample for the presence or absence of a concentration of the agent of interest,    wherein the presence of a concentration of the agent of interest is indicative of the presence of a neoplasm.    
   
   
       25 . A method of assessing an individual for the presence or absence of a neoplasm, comprising: 
 a) administering to the individual an agent of interest that comprises an imaging agent component and a targeting agent component, wherein the targeting agent component is selected from the group consisting of: : annexin A1, a derivative of annexin A1, a binding partner of annexin A1 , and a binding partner of a derivative of annexin A1;    b) taking a biopsy sample from the individual; and    c) assessing the biopsy sample for the presence or absence of a concentration of the agent of interest,    wherein the presence of a concentration of the agent of interest is indicative of the presence of a neoplasm.    
   
   
       26 . A method of delivering an imaging agent in a neoplasm-specific manner, comprising contacting the luminal surface and/or caveolae of vasculature with an agent of interest that comprises an imaging agent component and a targeting agent component, wherein the targeting agent component specifically binds to annexin A1, a derivative of annexin A1, a binding partner of annexin A1, and/or a derivative of a binding partner of annexin A1.  
   
   
       27 . A method of delivering an imaging agent in a neoplasm-specific manner, comprising contacting the luminal surface and/or caveolae of vasculature with an agent of interest that comprises an imaging agent component and a targeting agent component, wherein the targeting agent component comprises annexin A1, a derivative of annexin A1, a binding partner of annexin A1, and/or a derivative of a binding partner of annexin A1.  
   
   
       28 . A method of delivering an imaging agent in a neoplasm-specific manner to a tissue sample, comprising contacting the tissue sample with an agent of interest that comprises an imaging agent component and a targeting agent component, wherein the targeting agent component specifically binds to annexin A1 or a derivative of annexin A1.  
   
   
       29 . The method of  claim 28 , wherein the targeting agent component is selected from the group consisting of: annexin A1; derivative of annexin A1; an antibody to annexin1; and antibody to a derivative of annexin A1.  
   
   
       30 . A method of delivering an imaging agent in a neoplasm-specific manner to a tissue sample, comprising contacting the tissue sample with an agent of interest that comprises an imaging agent component and a targeting agent component, wherein the targeting agent component binds to a specific binding partner of annexin A1 or to a specific binding partner of a derivative of annexin A1.  
   
   
       31 . A method of delivering an imaging agent in a neoplasm-specific manner to a tissue sample, comprising contacting the tissue sample with an agent of interest that comprises an imaging agent component and a targeting agent component, wherein the targeting agent is selected from the group consisting of: annexin A1, a derivative of annexin A1, a specific binding partner of annexin A1, and a specific binding partner of a derivative of annexin A1.  
   
   
       32 . A method of assessing response to treatment with an annexin A1 therapeutic agent in an individual, comprising: 
 a) assessing the level of annexin A1 in a sample from the individual before treatment with an annexin A1 therapeutic agent;    b) assessing the level of annexin A1 in a sample from the individual during or after treatment with the annexin A1 therapeutic agent;    c) comparing the level before treatment with the level during or after treatment,    wherein a level of annexin A1 during or after treatment that is significantly lower than the level of annexin A1 before treatment, is indicative of efficacy of treatment with the annexin A1 therapeutic agent.    
   
   
       33 . A method of identifying an agent which alters activity of annexin A1 or an annexin A1 derivative, comprising: 
 a) contacting annexin A1 or annexin A1 derivative with an agent to be tested;    b) assessing the level of activity of annexin A1 or annexin A1 derivative; and    c) comparing the level of activity with a level of activity of annexin A1 or annexin A1 derivative in the absence of the agent,    wherein if the level of activity of the annexin A1 or annexin A1 derivative in the presence of the agent differs, by an amount that is statistically significant, from the level of activity of the annexin A1 or annexin A1 derivative in the absence of the agent, then the agent is an agent that alters activity of the annexin A1 or annexin A1 derivative.    
   
   
       34 . An agent which alters activity of annexin A1 or annexin A1 derivative, identifiable according to the method of  claim 33 .  
   
   
       35 . A method of delivering an agent to, into and/or across vascular endothelium in a neovasculature-specific manner, comprising contacting the luminal endothelial surface and/or caveolae of vasculature with an agent that specifically binds to annexin A1 or to a derivative of annexin A1.  
   
   
       36 . A method of treating angiogenesis or neovasculature in an individual, comprising administering to the individual an annexin A1 therapeutic agent.  
   
   
       37 . The method of  claim 36 , wherein the annexin A1 therapeutic agent is an antibody to annexin A1 or antibody to a derivative of annexin A1.  
   
   
       38 . The method of  claim 36 , wherein the annexin A1 therapeutic agent is annexin A1 or a derivative of annexin A1.  
   
   
       39 . The method of  claim 36 , wherein the annexin A1 therapeutic agent is an annexin A1 receptor or an annexin A1 binding partner.  
   
   
       40 . The method of  claim 36 , wherein the annexin A1 therapeutic agent is an agent that comprises an active agent component and a targeting agent component, wherein the active agent component is selected from the group consisting of: a radionuclide; a chemotherapeutic agent; an immune stimulatory agent; an anti-neoplastic agent: an anti-inflammatory agent; a pro-inflammatory agent; a pro-apoptotic agent; a pro-coagulant; a toxin; an antibiotic; a hormone; an enzyme; a protein (e.g., a recombinant protein or a recombinant modified protein) a carrier protein (e.g., albumin, modified albumin); a lytic agent; a small molecule; aptamers; cells, including modified cells; vaccine-induced or other immune cells; nanoparticles (e.g., albumin-based nanoparticles); transferrins; immunoglobulins; multivalent antibodies; lipids; lipoproteins; liposomes; an altered natural ligand; a gene or nucleic acid; RNA; siRNA; a viral or non-viral gene delivery vector; a prodrug; and a promolecule.  
   
   
       41 . The method of  claim 40 , wherein the targeting agent component is an agent that specifically binds to annexin A1 or to a derivative of annexin A1.  
   
   
       42 . The method of  claim 40 , wherein the targeting agent component is an antibody to annexin A1 or to a derivative of annexin A1.  
   
   
       43 . The method of  claim 40 , wherein the targeting agent component is annexin A1 or a derivative of annexin A1.  
   
   
       44 . The method of  claim 40 , wherein the targeting agent component is a specific binding partner of annexin A1 or a specific binding partner of a derivative of annexin A1.  
   
   
       45 . The method of  claim 40 , wherein the targeting agent component is an agent that binds to a specific binding partner of annexin A1 or to a specific binding partner of a derivative of annexin A1.  
   
   
       46 . A method of assessing an individual for the presence or absence of angiogenesis or neovasculature, comprising: 
 a) administering to the individual an agent of interest that comprises an imaging agent component and a targeting agent component, wherein the targeting agent component specifically binds to annexin A1 or a derivative of annexin A1, and    b) assessing the individual for the presence or absence of a concentration of the agent of interest,    wherein the presence of a concentration of the agent of interest is indicative of the presence of angiogenesis or neovasculature.    
   
   
       47 . The method of  claim 46 , wherein the targeting agent component is an antibody to annexin A1 or a derivative of annexin A1.  
   
   
       48 . A method of assessing an individual for the presence or absence of angiogenesis or neovasculature, comprising: 
 a) administering to the individual an agent of interest that comprises an imaging agent component and a targeting agent component, wherein the targeting agent component binds to a specific binding partner of annexin A1 or to a specific binding partner of a derivative of annexin A1, and    b) assessing the individual for the presence or absence of a concentration of the agent of interest,    wherein the presence of a concentration of the agent of interest is indicative of the presence of angiogenesis or neovasculature.    
   
   
       49 . A method of assessing an individual for the presence or absence of angiogenesis or neovasculature, comprising: 
 a) administering to the individual an agent of interest that comprises an imaging agent component and a targeting agent component, wherein the targeting agent component is selected from the group consisting of: : annexin A1, a derivative of annexin A1, a binding partner of annexin A1, and a binding partner of a derivative of annexin A1; and    b) assessing the individual for the presence or absence of a concentration of the agent of interest,    wherein the presence of a concentration of the agent of interest is indicative of the presence of angiogenesis or neovasculature.    
   
   
       50 . A method of assessing an individual for the presence or absence of angiogenesis or neovasculature, comprising: 
 a) administering to the individual an agent of interest that comprises an imaging agent component and a targeting agent component, wherein the targeting agent component binds to a specific binding partner of annexin A1 or to a specific binding partner of a derivative of annexin A1;    b) taking a biopsy sample from the individual;    c) assessing the biopsy sample for the presence or absence of a concentration of the agent of interest,    wherein the presence of a concentration of the agent of interest is indicative of the presence of angiogenesis or neovasculature.    
   
   
       51 . A method of assessing an individual for the presence or absence of angiogenesis or neovasculature, comprising: 
 a) administering to the individual an agent of interest that comprises an imaging agent component and a targeting agent component, wherein the targeting agent component is selected from the group consisting of: : annexin A1, a derivative of annexin A1, a binding partner of annexin A1, and a binding partner of a derivative of annexin A1;    b) taking a biopsy sample from the individual; and    c) assessing the biopsy sample for the presence or absence of a concentration of the agent of interest,    wherein the presence of a concentration of the agent of interest is indicative of the presence of angiogenesis or neovasculature.    
   
   
       52 . A method of delivering an imaging agent in a neovasculature-specific manner, comprising contacting the luminal surface and/or caveola of vasculature with an agent of interest that comprises an imaging agent component and a targeting agent component, wherein the targeting agent component specifically binds to annexin A1, a derivative of annexin A1, a binding partner of annexin A1, and/or a derivative of a binding partner of annexin A1.  
   
   
       53 . A method of delivering an imaging agent in a neovasculature-specific manner, comprising contacting the luminal surface and/or caveolae of vasculature with an agent of interest that comprises an imaging agent component and a targeting agent component, wherein the targeting agent component comprises annexin A1, a derivative of annexin A1, a binding partner of annexin A1, and/or a derivative of a binding partner of annexin A1.  
   
   
       54 . A method of delivering an imaging agent in a neovasculature-specific manner to a tissue sample, comprising contacting the tissue sample with an agent of interest that comprises an imaging agent component and a targeting agent component, wherein the targeting agent component specifically binds to annexin A1 or a derivative of annexin A1.  
   
   
       55 . The method of  claim 54 , wherein the targeting agent component is an antibody to annexin1 or to a derivative of annexin A1.  
   
   
       56 . A method of delivering an imaging agent in a neovasculature-specific manner to a tissue sample, comprising contacting the tissue sample with an agent of interest that comprises an imaging agent component and a targeting agent component, wherein the targeting agent component binds to a specific binding partner of annexin A1 or to a specific binding partner of a derivative of annexin A1.  
   
   
       57 . A method of delivering an imaging agent in a neovasculature-specific manner to a tissue sample, comprising contacting the tissue sample with an agent of interest that comprises an imaging agent component and a targeting agent component, wherein the targeting agent is selected from the group consisting of: annexin A1, a derivative of annexin A1, a specific binding partner of annexin A1, and a specific binding partner of a derivative of annexin A1.  
   
   
       58 . A method of increasing neovasculature in an individual, comprising administering to the individual an annexin A1 neovasculature agent.  
   
   
       59 . The method of  claim 58 , wherein the annexin A1 neovasculature agent is an agent that comprises an active agent component and a targeting agent component, wherein the targeting agent component is an agent that specifically binds to annexin A1 or to a derivative of annexin A1.  
   
   
       60 . The method of  claim 59 , wherein the targeting agent component is an antibody to annexin A1 or to a derivative of annexin A1.  
   
   
       61 . The method of  claim 59 , wherein the targeting agent component is annexin A1 or a derivative of annexin A1.  
   
   
       62 . The method of  claim 59 , wherein the targeting agent component is a specific binding partner of annexin A1 or a specific binding partner of a derivative of annexin A1.  
   
   
       63 . The method of  claim 59 , wherein the targeting agent component is an agent that binds to a specific binding partner of annexin A1 or to a specific binding partner of a derivative of annexin A1.  
   
   
       64 . A method of treating neoplasia in an individual, comprising administering to the individual an annexin A1 therpeutic agent that comprises annexin A1, wherein an immune response is generated against annexin A1.  
   
   
       65 . The method of  claim 64 , wherein the annexin A1 therapeutic agent further comprises a modified cell.