Tumor vascular marker-targeted vaccines
The present invention provides methods of immunizing a subject against a tumor, inhibiting tumor growth, inhibiting tumor recurrence, treating, suppressing the growth of, or decreasing the incidence of a tumor, overcoming tolerance to a tumor vasculature marker (TVM) in a subject comprising the step of administering a vaccine comprising a TVM or a nucleic acid encoding a TVM and related vaccines. The present invention also provides a method of targeting a tumor vasculature in a subject having a tumor comprising the step of contacting said subject with a labeled compound that binds a) a tumor vasculature marker (TVM) or b) a nucleic acid molecule encoding said TVM.
1. A method of inhibiting the growth of, suppressing the growth of, decreasing the incidence, and/or recurrence of a tumor in a subject, wherein the vasculature supplying said tumor comprises a tumor endothelial marker (TEM-1) protein, comprising the steps of:
a. identifying expression of said TEM-1 by said tumor by contacting said subject with a labeled compound that binds said TEM-1 or a nucleic acid molecule encoding said TEM-1;
b. detecting said label;
c. contacting said subject with an antibody to said TEM-1, wherein said antibody is labeled with a radionuclide to deliver cytotoxic radiation to tumor vasculature expressing said TEM-1; and
d. contacting said subject with a polypeptide comprising said TEM-1 protein or an immunogenic fragment thereof comprising an extracellular domain of TEM-1, said TEM-1 protein or said immunogenic fragment thereof fused to the N-terminal domain of fragment C of tetanus toxoid (DOM), or with a nucleic acid construct encoding said TEM-1 protein or said immunogenic fragment thereof, said nucleic acid fused in frame to a nucleic acid sequence encoding the N-terminal domain of fragment C of tetanus toxoid (DOM), to induce an immune response against said TEM-1.
2. The method of claim 1 , wherein said detecting step is performed using positron emission tomography (PET) scanning.
3. The method of claim 2 , wherein said detecting step also utilizes computed tomography (CT) or magnetic resonance imaging (MRI) scanning.