VEGF-conjugate combined methods for tumor vasculature targeting and tumor treatment

Abstract

The present invention relates generally to methods and compositions for targeting the vasculature of solid tumors using immunological- and growth factor-based reagents. In particular aspects, antibodies carrying diagnostic or therapeutic agents are targeted to the vasculature of solid tumor masses through recognition of tumor vasculature-associated antigens, such as, for example, through endoglin binding, or through the specific induction of endothelial cell surface antigens on vascular endothelial cells in solid tumors.

1 - 93 . (canceled)  
     
     
         94 . A method for treating an animal having a vascularized tumor, comprising: 
 administering to said animal an amount of a construct effective to treat said vascularized tumor, said construct comprising a selected therapeutic agent linked to VEGF, wherein said VEGF binds to a VEGF receptor expressed on the cell surfaces of intratumoral blood vessels of said vascularized tumor; and    administering to said animal a chemotherapeutic agent or an antitumor drug.    
     
     
         95 . The method of  claim 94 , wherein said construct is a fusion protein produced using recombinant DNA techniques.  
     
     
         96 . The method of  claim 94 , wherein said selected therapeutic agent is an anticellular agent that kills or suppresses the growth or cell division of tumor-associated endothelial cells of intratumoral blood vessels.  
     
     
         97 . The method of  claim 96 , wherein said anticellular agent is a chemotherapeutic agent, a radioisotope or a cytotoxin.  
     
     
         98 . The method of  claim 96 , wherein said anticellular agent is a steroid, an antimetabolite, an anthracycline, a vinca alkaloid, an antibiotic, an alkylating agent or an epipodophyllotoxin.  
     
     
         99 . The method of  96 , wherein said anticellular agent is a plant-, fungus- or bacteria-derived toxin.  
     
     
         100 . The method of  claim 99 , wherein said toxin is an A chain toxin, a ribosome inactivating protein, gelonin, α-sarcin, aspergillin, restrictocin, a ribonuclease, diphtheria toxin, Pseudomonas exotoxin, a bacterial endotoxin or the lipid A moiety of a bacterial endotoxin.  
     
     
         101 . The method of  claim 99 , wherein said toxin is ricin A chain.  
     
     
         102 . The method of  claim 101 , wherein said toxin is deglycosylated ricin A chain.  
     
     
         103 . The method of  claim 99 , wherein said toxin is gelonin.  
     
     
         104 . The method of  claim 94 , wherein said chemotherapeutic agent is an antimetabolite, an anthracycline, a vinca alkaloid or an antitumor alkylating agent.  
     
     
         105 . The method of  claim 94 , wherein said chemotherapeutic agent is selected from the group consisting of cytosine arabinoside, fluorouracil, methotrexate, aminopterin, mitomycin C, demecolcine, etoposide, mithramycin, chlorambucil, melphalan, doxorubicin, daunomycin, vinblastine, neocarzinostatin, macromycin, trenimon and α-amanitin.  
     
     
         106 . The method of  claim 94 , further comprising treating said animal with radiotherapy.  
     
     
         107 . The method of  claim 94 , wherein said animal has a squamous cell carcinoma, adenocarcinoma, small cell carcinoma, glioma or neuroblastoma.  
     
     
         108 . The method of  claim 94 , wherein said animal has a carcinoma of the lung, breast, ovary, stomach, liver, colon, rectum, cervix, uterus, endometrium, bladder or prostate.  
     
     
         109 . The method of  claim 94 , wherein said animal is a human cancer patient.