Targeting a Poor Prognosis Marker for Tumor Therapy Summary The purpose of this proposal is to develop a medical treatment for the elimination of metastatic cancers. According to the National Cancer Institute, the survival rate for many types of cancer has improved in recent years; however, it is still the second leading cause of death in the United States. This proposal describes an experimental design to verify the suitability of basigin-2 (also known as CD147 or EMMPRIN) as a cell surface target for an innovative tumor therapy. This project will accomplish important goals in determining the suitability of basigin-2 for further drug development: 1) Provide proof of internalization of the target moiety (basigin-2) by using an antibody to basigin-2, and 2) Demonstrate that there is specificity, both in terms of greater ability to target the tumor over normal (lower level) expression and that anti-basigin is specific for the target. In this Phase I grant, a cytotoxin will be produced that has two components: 1) anti-basigin to specifically target and internalize into basigin-2 positive cells, and 2) a toxin that will inhibit protein synthesis upon internalization by the antibody. This innovative approach will create a molecule that targets tumor cells, metastasis and angiogenesis, with the idea to not just slow tumor cell proliferation, but to eliminate tumors.
Public Health Relevance: Targeting a Poor Prognosis Marker for Tumor Therapy Narrative This project begins a new direction of potential treatment for a wide range of deadly cancers by targeting a molecule that is expressed on the surface of many tumor types with poor prognosis. While it is proposed to directly target these tumors through targeting the molecule, basigin-2, targeting of tumor metastasis and angiogenesis is also indicated, since basigin-2 plays important roles in those dangerous processes. The project builds on current technologies, but puts several together to go in a new, innovative direction.
Thesaurus Terms: "72-Kda Gelatinase; 72-Kda Type Iv Collagenase; 72kd Type Iv Collagenase; Antibodies; Binding; Binding (Molecular Function); Binding Proteins; Body Tissues; Boxing; Cd147 Antigen; Clg; Cancer Cell Line; Cancers; Cause Of Death; Cell Death; Cell Growth In Number; Cell Multiplication; Cell Proliferation; Cell Membrane; Cell Surface; Cell-Extracellular Matrix; Cells; Cellular Proliferation; Collaborations; Cytofluorometry, Flow; Cytoplasmic Membrane; Cytotoxin; Dna Synthesis Factor; Data; Disseminated Malignant Neoplasm; Dose; Drugs; Ecgf; Ecm; Endocytosis; Endothelial Cell Growth Factor; Experimental Designs; External Domain; Extracellular Domain; Extracellular Matrix; Fgf; Fibroblast Collagenase; Fibroblast Growth Factor; Fibroblast Growth Regulatory Factor; Fibroblasts; Flow Cytofluorometries; Flow Cytometry; Flow Microfluorimetry; Forecast Of Outcome; Gelatinase A; Gelatinase Neutrophil; Goals; Grant; Hbgf; Ht7 Antigen; Illinois; Individual; Interstitial Collagenase; Intervention; Intervention Strategies; Ligand Binding Protein; Lytotoxicity; Mmp-1; Mmp-1fibroblast Collagenase; Mmp-2; Mmp-3; Mmp1; Mmp2; Mmp3; Mmps; Malignant Neoplasms; Malignant Tumor; Mammals, Mice; Matrix Metalloproteinase 3; Matrix Metalloproteinase-1; Matrix Metalloproteinase-2; Matrix Metalloproteinases; Medical; Medication; Metastasis; Metastasize; Metastatic Cancer; Metastatic Malignant Neoplasm; Metastatic Neoplasm; Metastatic Tumor; Mice; Microfluorometry, Flow; Moab, Clinical Treatment; Modeling; Molecular Interaction; Molecular Marker Of Prognosis; Monoclonal Antibodies; Murine; Mus; Nci; Nci Organization; National Cancer Institute; Neoplasm Metastasis; Pex; Peptide Biosynthesis, Ribosomal; Pharmaceutic Preparations; Pharmaceutical Preparations; Phase; Plasma Membrane; Play; Process; Prognosis; Prognosis Marker; Prognostic Marker; Protein Biosynthesis; Protein Biosynthesis, Ribosomal; Protein Synthesis Inhibition; Protein Synthesis, Ribosomal; Proteins; Recombinants; Resistance; Ribosomes; Role; Secondary Neoplasm; Secondary Tumor; Serum Proteins; Specificity; Strepavidin; Streptavidin; Stromelysin; Stromelysin 1; Surface; Survival Rate; System; System, Loinc Axis 4; Transin; Technology; Tissues; Toxin; Transin-1; Tumor Cell; Tumor Cell Migration; United States; Universities; Vascular Endothelial Cell; Work; Angiogenesis; Basigin; Basigin-2; Cancer Metastasis; Cancer Type; Collagenase Activating Protein; Cytotoxicity; Design; Designing; Drug Development; Drug/Agent; Experiment; Experimental Research; Experimental Study; Flow Cytophotometry; Gene Product; Improved; In Vivo; Innovate; Innovation; Innovative; Interventional Strategy; Malignancy; Necrocytosis; Neoplasm/Cancer; Neoplastic Cell; Outcome Forecast; Plasmalemma; Procollagenase Activator; Protein Synthesis; Proteoglycanase; Public Health Relevance; Research Study; Resistant; Response; Social Role; Tumor; Tumor Growth"
