Methods and Compositions for Cancer Diagnosis

Abstract

The present invention provides reagents and methods for detecting cancer precancerous lesions in a patient.

1 . A method for detecting pancreatic cancer in a patient, or for determining a risk for pancreatic cancer development in a patient comprising one of:
 (a) (i) administering a detectable Thy-1 binding molecule to a patient at risk of having or developing pancreatic cancer, under conditions suitable to promote binding complex formation between the Thy-1 binding molecule and Thy-1 present in pancreatic tumor neovasculature or a precancerous lesion; and (ii) detecting the presence or absence of the binding complexes; wherein the presence of an increased number of the binding complexes compared to control is indicative of the presence of pancreatic cancer in the patient or indicates a risk of pancreatic cancer development in the patient, or   (b) (i) administering a detectable binding molecule to a patient at risk of having or developing pancreatic cancer, wherein the binding molecule is selected from the group consisting of (a) MMRN1 binding molecules, (b) MRC2 binding molecules, (c) NRP1 binding molecules, and/or (d) VCAM1 binding molecules, under conditions suitable to promote binding complex formation between the binding molecule and a binding molecule target present in pancreatic tumor neovasculature or a recancerous lesion; and (ii) detecting the presence or absence of the binding complexes; wherein the presence of an increased number of the binding complexes compared to control is indicative of the presence of pancreatic cancer in the patient or indicates a risk of pancreatic cancer development in the patient.   
     
     
         2 . The method of  claim 1 , wherein the molecule is selected from the group consisting of anti-human Thy-1 antibodies and a protein comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:1-20. 
     
     
         3 . The method of  claim 1 , wherein the binding molecule is attached to the surface of a microbubble. 
     
     
         4 . The method of  claim 1 , wherein the detecting is carried out by ultrasound molecular imaging. 
     
     
         5 . The method of  claim 1 , wherein the presence of the binding complexes is indicative of the presence of precancerous lesions, and thus indicative of a risk of pancreatic cancer development in the patient. 
     
     
         6 . The method of  claim 1 , wherein the presence of the binding complexes is indicative of the presence of pancreatic ductal adenocarcinoma in the patient. 
     
     
         7 . (canceled) 
     
     
         8 . A method for determining efficacy of pancreatic cancer therapy in a patient, comprising one of:
 (a) (i) administering a detectable Thy-1 binding molecule to a patient undergoing or who has previously undergone pancreatic cancer therapy, under conditions suitable to promote binding of the Thy-1 binding molecule to Thy-1 in the pancreatic tumor neovasculature to form a binding complex; and (ii) detecting the presence or absence of binding complexes; wherein the presence or absence of binding complexes is indicative of the efficacy of the anti-cancer therapy in the patient; or   (b) (i) administering a detectable binding molecule selected from the group consisting of (i) MMRN1 binding molecules, (ii) MRC2 binding molecules, (iii) NRP1 binding molecules, and (iv) VCAM1 binding molecules, to a patient undergoing or who has previously undergone pancreatic cancer therapy, under conditions suitable to promote binding complex formation between the binding molecule and its target present in pancreatic tumor neovasculature to form a binding complex; and (ii) detecting the presence or absence of the binding complexes; wherein the presence or absence of binding complexes is indicative of the efficacy of the anti-cancer therapy in the patient.   
     
     
         9 . (canceled) 
     
     
         10 . A composition, comprising:
 (a) a first microbubble; and   (b) a plurality of Thy-1 binding molecules attached to a surface of the first microbubble.   
     
     
         11 . The composition of  claim 10 , wherein the Thy-I binding molecules are selected from the group consisting of anti-human Thy-1 antibodies and a protein comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:1-20. 
     
     
         12 . The composition of  claim 10 , wherein the first microbubble further comprises a plurality of other binding molecules attached to a surface of the first microbubble, wherein the other binding molecules are selected from the group consisting of (a) VEGFR2 binding molecules, (b) MMRN1 binding molecules, (c) MRC2 binding molecules, (d) NRP1 binding molecules, and/or (e) VCAM1 binding molecules. 
     
     
         13 . The composition of  claim 10 , wherein the composition further comprises a second microbubble, wherein the second microbubble has attached to its surface a plurality of other binding molecules, wherein the other binding molecules are selected from the group consisting of (a) VEGFR2 binding molecules, (b) MMRN1 binding molecules, (c) MRC2 binding molecules, (d) NRP1 binding molecules, and/or (e) VCAM1 binding molecules. 
     
     
         14 . The composition of  claim 10 , wherein the composition comprises at least 10 7  first microbubbles and/or second microbubbles. 
     
     
         15 . The composition of  claim 10 , further comprising one or more anti-cancer therapeutics on or in the first microbubble and/or the second microbubble. 
     
     
         16 . (canceled) 
     
     
         17 . A method for detecting cancer in a patient, or for determining a risk for cancer development in a patient comprising:
 (a) administering the composition of  claim 10  to a patient at risk of having or developing cancer, under conditions suitable to promote binding complex formation between the binding molecules and targets of the binding molecules present in neovasculature of the tumor or a precancerous lesion; and   (b) detecting a presence or absence of the binding complexes using ultrasound molecular imaging; wherein the presence of an increased number of the binding complexes compared to control is indicative of the presence of cancer in the patient or indicates a risk of cancer development in the patient.   
     
     
         18 . The method of  claim 17 , wherein the binding complex comprises a complex between the binding molecule and binding molecule target present in neovasculature of a tumor or a precancerous lesion. 
     
     
         19 . The method of  claim 17 , wherein the presence of the binding complexes is indicative of the presence of a precancerous lesion, and thus indicative of a risk of cancer development in the patient. 
     
     
         20 . The method of  claim 17 , wherein the presence of the binding complexes is indicative of the presence of cancer in the patient.