Molecular lymphatic mapping of sentinel lymph nodes

Abstract

The present invention describes a method for identification and labeling of sentinel lymph nodes (SLNs) and the presence or absence of lymph node metastases as an important diagnostic and prognostic factor in early stage cancers of all types. The method, know as Molecular Lymphatic Mapping, uses traditional dye/radioactive tracer based techniques in conjunction with a nucleic acid marker to identify and label the SLN, not only for current diagnostic methods, but for archival purposes. In addition, MLM can be used to deliver a therapeutic gene or genes to the SLN to activate tumor immunity to tumor cells, and/or to inhibit tumor metastases. The methods may be combined with therapeutic intervention including chemotherapy and radiotherapy.

1 - 59 . (canceled) 
     
     
         60 . A method for treating cancer in a subject comprising:
 (a) administering a composition comprising a marker nucleic acid segment to a human subject regional to a sentinel lymph node;   (b) determining the presence or absence of the marker nucleic acid segment in a lymph node, wherein the presence of said marker nucleic acid segment in the lymph node identifies the lymph node as a sentinel lymph node; and   (c) providing a gene therapy to the subject, whereby the cancer is treated.   
     
     
         61 . The method of  claim 60 , wherein gene therapy comprises targeting a sentinel lymph node with a gene therapy vector comprising a cancer therapeutic coding region operably linked to a promoter active in eukaryotic cells. 
     
     
         62 . The method of  claim 61 , wherein the gene therapy vector comprises a nucleic acid segment encoding a tumor suppressor, an inducer of apoptosis, a cytokine, a cell cycle regulator, a toxin, or a hormone. 
     
     
         63 . The method of  claim 61 , wherein the promoter is a constitutive promoter, a tissue specific promoter or an inducible promoter. 
     
     
         64 . The method of  claim 61 , wherein the gene therapy vector is a non-viral vector. 
     
     
         65 . The method of  claim 61 , wherein the gene therapy vector is a viral vector. 
     
     
         66 . The method of  claim 65 , wherein the viral vector is a herpesviral vector, an adenoviral vector, a retroviral vector, a polyoma viral vector or a poxviral vector. 
     
     
         67 . The method of  claim 61 , wherein the gene therapy vector is in a liposome. 
     
     
         68 . The method of  claim 60 , wherein the cancer is a solid tumor cancer selected from the group consisting of breast cancer, gastrointestinal cancer, melanoma, lymphoma, squamous carcinoma, merkel cell cancer, colorectal cancer, pancreatic cancer, gastric cancer, thyroid cancer, renal cancer, bladder cancer, prostate cancer, esophageal cancer, vulvar cancer, ovarian cancer, penile cancer, head & neck cancer and lung cancer. 
     
     
         69 . The method of  claim 60 , further comprising surgical removal of primary tumor tissue. 
     
     
         70 . The method of  claim 60 , further comprising surgical removal of a sentinel lymph node. 
     
     
         71 . The method of  claim 70 , further comprising surgical removal of multiple lymph nodes. 
     
     
         72 . The method of  claim 70 , further comprising assessing the presence or absence of metastatic cells in the sentinel lymph node. 
     
     
         73 . The method of  claim 60 , wherein the marker nucleic acid segment is a prokaryotic nucleic acid segment. 
     
     
         74 . The method of  claim 60 , wherein the marker nucleic acid segment is a plant nucleic acid segment. 
     
     
         75 . The method of  claim 74 , wherein the plant nucleic acid segment is a rice nucleic acid segment. 
     
     
         76 . The method of  claim 60 , wherein determining the presence or absence of the marker nucleic acid segment comprises nucleic acid hybridization to said marker nucleic acid segment. 
     
     
         77 . The method of  claim 76 , further comprising nucleic acid amplification of said marker nucleic acid segment. 
     
     
         78 . The method of  claim 76 , wherein the nucleic acid hybridization comprises hybridization of a labeled probe to nucleic acids isolated from cells of the removed lymph node.