Compositions and methods for identifying and targeting cancer cells of alimentary canal origin

Abstract

Screening and diagnostic reagents, kits and methods for metastatic colorectal cancer or primary and/or metastatic stomach or esophageal cancer are disclosed. Compounds, compositions and methods of treating patients with metastatic colorectal cancer or stomach or esophageal cancer and for imaging metastatic colorectal cancer or stomach or esophageal tumors in vivo are disclosed. Compositions and methods for delivering active compounds such as drugs, gene therapeutics and antisense compounds to metastatic colorectal cancer or stomach or esophageal cells are disclosed. Vaccines compositions and methods of for treating and preventing metastatic colorectal cancer or primary and/or metastatic stomach or esophageal cancer are disclosed.

1 . An in vitro method of screening an individual for metastatic colorectal cancer cells or primary and/or metastatic stomach or esophageal cancer cells comprising the steps of examining a sample of extraintestinal tissue and/or body fluids from an individual to determine whether SI is being expressed by cells in said sample wherein expression of said SI indicates a possibility of metastatic colorectal cancer cells or primary and/or metastatic stomach or esophageal cancer cells in said sample. 
     
     
         2 . The method of  claim 1  wherein expression of said SI by said cells is determined by detecting the presence of SI gene transcription product. 
     
     
         3 . The method of  claim 1  wherein expression of said SI by said cells is determined by polymerase chain reaction wherein said sample is contacted with primers that selectively-amplify SI gene transcript or cDNA generated therefrom. 
     
     
         4 . The method of  claim 1  wherein expression of said SI by said cells is determined by immunoassay wherein said sample is contacted with antibodies that specifically bind to SI gene translation product. 
     
     
         5 . The method of  claim 1  wherein said sample is body fluid. 
     
     
         6 . The method of  claim 1  wherein said sample is blood. 
     
     
         7 . The method of  claim 1  wherein said sample is lymphatic tissue and/or fluid. 
     
     
         8 . The method of  claim 1  wherein said sample is a lymph node sample. 
     
     
         9 . The method of  claim 1  wherein the individual has previously been diagnosed with having colorectal, stomach or esophageal cancer. 
     
     
         10 . The method of  claim 1  wherein the individual has previously been diagnosed with and treated for colorectal, stomach or esophageal cancer 
     
     
         11 . An in vitro method of screening an individual for metastatic colorectal cancer cells or primary and/or metastatic stomach or esophageal cancer cells comprising the steps of examining a sample of extraintestinal tissue and/or body fluids from an individual to determine whether SI gene transcription or translation product is present in said sample wherein the presence of SI gene transcription or translation product in said sample indicates that the individual may have metastatic colorectal cancer cells or primary and/or metastatic stomach or esophageal cancer cells in said sample. 
     
     
         12 . The method of  claim 10  comprising the steps of examining a sample of extraintestinal tissue and/or body fluids from an individual to determine whether SI gene transcription product is present in said sample. 
     
     
         13 . The method of  claim 12  wherein the presence of SI gene transcription product is determined by polymerase chain reaction wherein said sample is contacted with primers that selectively amplify SI gene transcript or cDNA generated therefrom. 
     
     
         14 . The method of  claim 11  wherein the presence of SI gene translation product is determined by immunoassay wherein said sample is contacted with antibodies that specifically bind to SI gene translation product. 
     
     
         15 . The method of  claim 11  wherein said sample is body fluid. 
     
     
         16 . The method of  claim 11  wherein said sample is blood. 
     
     
         17 . The method of  claim 11  wherein said sample is lymphatic tissue and/or fluid. 
     
     
         18 . The method of  claim 11  wherein said sample is a lymph node sample. 
     
     
         19 . The method of  claim 11  wherein the individual has previously been diagnosed with having colorectal, stomach or esophageal cancer. 
     
     
         20 . The method of  claim 11  wherein the individual has previously been diagnosed with and treated for colorectal, stomach or esophageal cancer 
     
     
         21 . An in vitro method of confirming that a tumor cell removed from a patient suspected of having colorectal, stomach or esophageal cancer cells is a colorectal, stomach or esophageal tumor cell comprising the step of determining whether a tumor cell expresses SI wherein expression of SI indicates that the tumor cell is a stomach or esophageal tumor cell. 
     
     
         22 . The method of  claim 21  wherein expression of SI by said tumor cell is determined by detecting the presence of SI gene transcription product. 
     
     
         23 . The method of  claim 21  wherein expression of SI by said tumor cell is determined by polymerase chain reaction wherein mRNA from said tumor cell or cDNA generated therefrom is contacted with primers that selectively amplify SI gene transcript or cDNA generated therefrom. 
     
     
         24 . The method of  claim 21  wherein expression of SI by said tumor cell is determined by immunoassay wherein protein from said tumor cell is contacted with antibodies that specifically bind to SI gene translation product. 
     
     
         25 . A method of diagnosing an individual who has stomach cancer comprising the steps of examining a sample of stomach tissue to detect the presence of SI transcript or translation product wherein the presence of SI transcript or translation product in a stomach sample indicates stomach cancer. 
     
     
         26 . The method of  claim 25  comprising the steps of examining said sample of stomach tissue to determine whether SI gene transcription product is present in said sample. 
     
     
         27 . The method of  claim 26  wherein the presence of SI gene transcription product is determined by polymerase chain reaction wherein said sample is contacted with primers that selectively amplify SI gene transcript or cDNA generated therefrom. 
     
     
         28 . The method of  claim 26  wherein the presence of SI gene translation product is determined by immunoassay wherein said sample is contacted with antibodies that specifically bind to SI gene translation product. 
     
     
         29 . A method of diagnosing an individual who has esophageal cancer comprising the steps of examining a sample of esophagus tissue to detect the presence of SI transcript or translation product wherein the presence of SI transcript or translation product in an esophageal sample indicates esophageal cancer. 
     
     
         30 . The method of  claim 29  comprising the steps of examining said sample of esophageal tissue to determine whether SI gene transcription product is present in said sample. 
     
     
         31 . The method of  claim 30  wherein the presence of SI gene transcription product is determined by polymerase chain reaction wherein said sample is contacted with primers that selectively amplify SI gene transcript or cDNA generated therefrom. 
     
     
         32 . The method of  claim 29  wherein the presence of SI gene translation product is determined by immunoassay wherein said sample is contacted with antibodies that specifically bind to SI gene translation product. 
     
     
         33 . A kit for diagnosing an individual who has colorectal, stomach and/or esophageal cancer comprising either:
 a) a container comprising polymerase chain reaction primers that selectively amplify SI gene transcript or cDNA generated therefrom;
 and one or more of:
 a container comprising a positive PCR assay control sample, a container comprising a negative PCR assay control sample, instructions for obtaining and/or processing a sample, instructions for performing a PCR diagnostic assay, and photographs or illustrations depicting a positive result and/or a negative result of a PCR diagnostic assay; or 
 
   b) a container comprising antibodies that specifically bind to SI gene translation product;
 and one or more of:
 a container comprising a positive immunoassay control sample, a container comprising a negative immunoassay control sample, instructions for obtaining and/or processing a sample, instructions for performing an immuno diagnostic assay, and photographs or illustrations depicting a positive result and/or a negative result of an immuno diagnostic assay. 
 
   
     
     
         34 . A method of treating an individual suspected of suffering from metastasized colorectal cancer, or primary and/or stomach or espophageal cancer comprising the steps of administering to said individual a therapeutically effective amount of a composition comprising:
 i) an SI ligand; and,   ii) an active agent.   
     
     
         35 . The method of  claim 34  wherein the SI ligand is conjugated to the active agent. 
     
     
         36 . The method of  claim 34  wherein said an active agent is selected from the group consisting of: methotrexate, doxorubicin, daunorubicin, cytosinarabinoside, etoposide, 5-4 fluorouracil, melphalan, chlorambucil, cis-platinum, vindesine, mitomycin, bleomycin, purothionin, macromomycin, 1,4-benzoquinone derivatives, trenimon, ricin, ricin A chain,  Pseudomonas  exotoxin, diphtheria toxin,  Clostridium perfringens  phospholipase C, bovine pancreatic ribonuclease, pokeweed antiviral protein, abrin, abrin A chain, cobra venom factor, gelonin, saporin, modeccin, viscumin, volkensin, alkaline phosphatase, nitroimidazole, metronidazole, misonidazole,  47 Sc,  67 Cu,  90 Y,  109 Pd,  123 I,  125 I,  131 I,  186 Re,  188 Re,  199 Au,  211 At,  212 Pb,  212 B,  32 P and  33 P,  71 Ge,  77 As,  103 Pb,  105 Rh,  111 Ag,  119 Sb,  121 Sn,  131 Cs,  143 Pr,  161 Tb,  177 Lu,  191 Os,  193M Pt,  197 Hg,  43 K,  52 Fe,  57 Co,  67 Cu,  67 Ga,  68 Ga,  77 Br,  81 Rb/ 81M Kr,  87M Sr,  99M Tc,  111 In,  113M In,  123 I,  125 I,  127 Cs,  129 Cs,  131 I,  132 I,  197 Hg,  203 Pb and  206 Bi. 
     
     
         37 . A method of radioimaging metastasized colorectal cancer cells comprising the steps of administering to an individual a composition comprising an SI ligand linked to a detectable agent. 
     
     
         38 . The method of  claim 37  wherein said detectable agent is selected from the group consisting of:  47 Sc,  67 Cu,  90 Y,  109 Pd,  123 I,  125 I,  131 I,  186 Re,  188 Re,  199 Au,  211 At,  212 Pb,  212 B,  32 P and  33 P,  71 Ge,  77 As,  103 Pb,  105 Rh,  111 Ag,  119 Sb,  121 Sn,  131 Cs,  143 Pr,  161 Tb,  177 Lu,  191 Os,  193M Pt,  197 Hg,  43 K,  52 Fe,  57 Co,  67 Cu,  67 Ga,  68 Ga,  77 Br,  81 Rb/ 81M Kr,  87M Sr,  99M Tc,  111 In,  113M In,  123 I,  125 I,  127 Cs,  129 Cs,  131 I,  132 I,  197 Hg,  203 Pb and  206 Bi.