Tumor specific antibodies and uses therefor

Abstract

Provided are isolated antibodies, and fragments and derivatives thereof, which bind to tumor antigens. Also provided are compositions and delivery agents that include the disclosed antibodies and fragments and derivatives thereof; cells that produce the same; methods for producing the same; methods of using the same for detecting, targeting, and/or treating tumors and/or metastatic cells derived therefrom and/or tumor stem cells; and methods for predicting the recurrence of cancer in a subject.

What is claimed is: 
     
         1 . A delivery vehicle for use in targeted delivery of an active agent to a tumor cell, the delivery vehicle comprising a targeting agent that comprises an isolated antibody, or a fragment or derivative thereof, comprising the complementarity determining regions (CDRs) of monoclonal antibody TAB-004. 
     
     
         2 . The delivery vehicle of  claim 1 , wherein the active agent comprises a radioactive molecule, a radionuclide, a sensitizer molecule, an imaging reagent, a radioisotope, a toxin, a cytotoxin, an anti-angiogenic agent, an anti-tumor agent, a chemotherapeutic agent, an immunomodulator, a cytokine, a reporter group, or a combination thereof. 
     
     
         3 . A method of producing an antibody that is specific for a tumor-associated epitope of a human MUC1 polypeptide, comprising:
 (a) immunizing a mouse with a protein lysate prepared from a PDA.MUC1.TG mouse, wherein the PDA.MUC1.TG mouse expresses human MUC1 and mutated K-rasG12D tumor antigens;   (b) fusing spleen cells from the immunized mouse with myeloma cells to produce a plurality of hybridomas; and   (c) screening the one or more of the plurality of hybridomas to identify a hybridoma that produces an antibody that specifically binds to tumor-associated epitope of a human MUC1 polypeptide.   
     
     
         4 . A method for purifying a cancer stem cell, the method comprising:
 (a) providing a population of cells suspected of comprising cancer stem cells;   (b) identifying a subpopulation of the cells that bind to an antibody, or a fragment or derivative thereof, comprising the CDRs of monoclonal antibody TAB-004; and   (c) purifying the subpopulation.   
     
     
         5 . The method of  claim 4 , wherein the population of cells comprises circulating cells isolated from a subject that has a tumor and/or a cancer. 
     
     
         6 . The method of  claim 4 , further comprising removing lineage-positive (lin + ) cells from the population of cells before the identifying step and/or after the purifying step.