Using a dye or radioactive tracer in conjunction with nucleic acid marker; cancer diagnosis and prognosis; drug delivery, gene therapy, activation of tumor immunity and inhibiting metastasis
Inventors
Hoon, Dave S. B. • Taback, Bret
Assignees
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Publication Number
US-7897336-B2
Publication Date
2011-03-01
Expiration Date
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.
Core Innovation
Molecular Lymphatic Mapping (MLM) identifies sentinel lymph nodes (SLNs) and detects lymph node metastases in early solid cancers by administering a marker nucleic acid segment near a sentinel lymph node in a human subject and determining whether the marker nucleic acid segment is present or absent in a lymph node. The presence of the marker nucleic acid segment in the lymph node identifies the lymph node as a sentinel lymph node.
The marker nucleic acid segment is provided as an example using rice DNA/plasmid or a linear rice DNA fragment. After lymph node removal, detection includes nucleic acid detection approaches such as PCR/RT-PCR, quantitative real-time PCR, and in situ hybridization, including probe localization in SLN subcapsular/paratrabecular sinus.
The disclosed approach includes validation of marker detection in frozen and paraffin-embedded rat sentinel lymph nodes and mesenteric lymph nodes, with histochemical/in situ verification of marker localization. Quantitative marker copy numbers can be reported using real-time PCR, while in situ hybridization supports localization verification, and the document further discusses therapeutic use of MLM for delivering therapeutic genes to SLNs to activate tumor immunity and/or inhibit metastasis.
Claims Coverage
The independent claim covers a method for identifying sentinel lymph nodes using a marker nucleic acid segment administered near a sentinel lymph node to a human subject, followed by determining the presence or absence of the marker in a lymph node, where presence identifies the lymph node as a sentinel lymph node. The dependent claims refine the independent claim with additional features such as administration context, marker nucleic acid type, detection workflow, optional labeling/tracer choices, histopathology modalities, and linking sentinel-node findings to metastatic-cell presence for treatment/staging decisions. Independent claims explicitly provided: 1.
Sentinel lymph node identification with marker nucleic acid presence
Administering a composition comprising a marker nucleic acid segment to a human subject regional to a sentinel lymph node; determining the presence or absence of the marker nucleic acid segment in a lymph node; wherein presence of said marker nucleic acid segment in the lymph node identifies the lymph node as a sentinel lymph node.
Overall claim coverage centers on the sentinel-node identification concept based on whether a marker nucleic acid segment is present or absent in a removed lymph node, with additional disclosed claim refinements addressing marker form, optional labeling/tracer options, nucleic acid detection workflows, and downstream assessment of metastatic cells in sentinel lymph nodes.
Stated Advantages
Allows identification of sentinel lymph nodes by determining whether a marker nucleic acid segment is present or absent in a lymph node.
Enables detection of lymph node metastases in early solid cancers using the marker nucleic acid segment approach.
Supports quantitative reporting of marker copy numbers using real-time PCR.
Provides localization verification of the marker in lymph node tissue using histochemical/in situ hybridization approaches.
Potentially enables therapeutic application by delivering therapeutic genes to SLNs to activate tumor immunity and/or inhibit metastasis.
Documented Applications
Using Molecular Lymphatic Mapping (MLM) to identify sentinel lymph nodes (SLNs) and detect lymph node metastases in early solid cancers.
Providing a therapeutic use case in which MLM can deliver therapeutic genes to SLNs to activate tumor immunity and/or inhibit metastasis.
Using sentinel-node findings that include whether metastatic cells are present in a sentinel lymph node as a basis for a treatment decision.
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