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Substance P-saporin for bone cancer pain in dogs: Can man’s best friend solve the lost in translation problem in analgesic development?
Hayashida K (2013) Substance P-saporin for bone cancer pain in dogs: Can man’s best friend solve the lost in translation problem in analgesic development?. Anesthesiology 119(5):999-1000. doi: 10.1097/ALN.0b013e3182a951a2
Summary: This editorial describes the SP-SAP papers in this latest issue of Anesthesiology. The results of the paper are discussed, and the potential in using companion dogs for pain models is emphasized. While most pain models have been rodent-based, companion dogs provide models for chronic pain due to natural causes such as cancer and arthritis, along with frequent opportunity for behavioral assessments by the owner. Such assessments can be done without stress to the animal.
Related Products: SP-SAP (Cat. #IT-07)
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Saporin conjugated monoclonal antibody to the transcobalamin receptor TCblR/320 is effective in targeting and destroying cancer cells.
Quadros EV, Nakayama Y, Sequeira JM (2013) Saporin conjugated monoclonal antibody to the transcobalamin receptor TCblR/320 is effective in targeting and destroying cancer cells. J Cancer Ther 4(6):1074-1081. doi: 10.4236/jct.2013.46122
Summary: Although the transcobalamin receptor (TCb1R) is expressed in most cell types, the expression levels are increased in actively proliferating cells, and decreased in quiescent cells. This expression profile makes the TCb1R an attractive target for cancer therapy. The authors used a custom conjugate of antibodies generated against the TCb1R and saporin to eliminate cancer cell lines in culture. When applying the conjugate to cells in a dosing range of 0.156-5 nM, 2.5 nM was found to have the optimal effect. Given that the level of toxicity was determined by the level of TCb1R expression, targeting the TCb1R may have potential as part of a cancer treatment strategy.
Related Products: Custom Conjugates
Photochemical internalization (PCI) of immunotoxins targeting CD133 is specific and highly potent at femtomolar levels in cells with cancer stem cell properties.
Bostad M, Berg K, Hogset A, Skarpen E, Stenmark H, Selbo PK (2013) Photochemical internalization (PCI) of immunotoxins targeting CD133 is specific and highly potent at femtomolar levels in cells with cancer stem cell properties. J Control Release 168(3):317-326. doi: 10.1016/j.jconrel.2013.03.023
Summary: Targeted therapies for cancer can be trapped in the lysosome and compartmentalized away from the target. Photochemical internalization is a method to increase the efficacy of these compounds by releasing the therapeutic portion of the molecule from the endocytic vesicles to the cytosol by the use of light. The authors demonstrate this method on cells expressing the cancer stem cell marker CD133. Biotinylated antibodies against CD133 were combined with Streptavidin-ZAP (Cat. #IT-27) and applied to cell lines.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
A novel model for evaluating therapies targeting human tumor vasculature and human cancer stem-like cells.
Burgos-Ojeda D, McLean K, Bai S, Pulaski H, Gong Y, Silva I, Skorecki K, Tzukerman M, Buckanovich RJ (2013) A novel model for evaluating therapies targeting human tumor vasculature and human cancer stem-like cells. Cancer Res 73(12):3555-3565. doi: 10.1158/0008-5472.CAN-12-2845
Objective: To evaluate tumor vascular markers (TVM) expression in a human embryonic stem cell–derived teratoma (hESCT) tumor model previously shown to have human vessels.
Summary: The model tested represents a useful tool to test anti-human TVM therapy and evaluate in vivo human CSC tumor biology.
Usage: In vitro – Anti-THY1-SAP (biotinylated Anti-THY1 mixed equimolar with Streptavidin-ZAP) was incubated with mesenchymal stem cells (MSC); resulting in statistically significant MSC death. In vivo – Anti-THY1-SAP or control (Rat IgG-SAP) was administered intravenously. Treated ovarian tumors showed delayed growth and significant reduction in central tumor viability.
Related Products: Streptavidin-ZAP (Cat. #IT-27), Rat IgG-SAP (Cat. #IT-17)
Featured Article: Antibodies to glycosphingolipids: An attractive tool for targeted delivery of cytotoxic agents to tumor cells
Daniotti JL (2013) Featured Article: Antibodies to glycosphingolipids: An attractive tool for targeted delivery of cytotoxic agents to tumor cells. Targeting Trends 14(2)
Related Products: Mab-ZAP (Cat. #IT-04)
Read the featured article in Targeting Trends.
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Combining phenotypic and proteomic approaches to identify membrane targets in a ‘triple negative’ breast cancer cell type.
Rust S, Guillard S, Sachsenmeier K, Hay C, Davidson M, Karlsson A, Karlsson R, Brand E, Lowne D, Elvin J, Flynn M, Kurosawa G, Hollingsworth R, Jermutus L, Minter R (2013) Combining phenotypic and proteomic approaches to identify membrane targets in a ‘triple negative’ breast cancer cell type. Mol Cancer 12:11. doi: 10.1186/1476-4598-12-11
Summary: The authors investigated a phenotypic antibody screening technique, in which antibodies are selected by function rather than target specificity. One facet of the screening procedure for hybridomas generated using a cancer cell line as antigen was the use of Mab-ZAP (Cat. #IT-04) to assess cell binding and internalization.
Related Products: Mab-ZAP (Cat. #IT-04)
Targeted delivery of immunotoxin by antibody to ganglioside GD3: A novel drug delivery route for tumor cells.
Torres Demichelis V, Vilcaes AA, Iglesias-Bartolome R, Ruggiero FM, Daniotti JL (2013) Targeted delivery of immunotoxin by antibody to ganglioside GD3: A novel drug delivery route for tumor cells. PLoS One 8(1):e55304. doi: 10.1371/journal.pone.0055304
Summary: The authors used the mouse monoclonal antibody R24 against ganglioside G3 with Mab-ZAP (Cat. #IT-04) to test the viability of ganglioside G3 as a cancer therapy target. Varying concentrations of R24 were used on various cell lines with either 0.95 nM or 9.5 nM Mab-ZAP depending on the cell line.
Related Products: Mab-ZAP (Cat. #IT-04)
Efficacy and toxicity of a CD22-targeted antibody-saporin conjugate in a xenograft model of non-Hodgkin’s lymphoma.
Kato J, O’Donnell RT, Abuhay M, Tuscano JM (2012) Efficacy and toxicity of a CD22-targeted antibody-saporin conjugate in a xenograft model of non-Hodgkin’s lymphoma. Oncoimmunology 1(9):1469-1475. doi: 10.4161/onci.21815
Summary: CD22 is a B-cell-specific antigen found on many B-cell malignancies. It is not expressed by stem cell precursors, and is rapidly internalized when bound by an antibody. In this work, the authors use a custom conjugate of anti-CD22 (mAb HB22.7) and saporin in a cytotoxicity assay on non-Hodgkin’s lymphoma cell lines, as well as in a mouse tumor model. The dosing for the tumor model was 1 mg conjugate per kg of animal. Mouse IgG-SAP (Cat. #IT-18) was used as a control. The results indicate that CD22 is a potential therapeutic target for cancer therapy.
Related Products: Mouse IgG-SAP (Cat. #IT-18), Custom Conjugates
CD22 antigen is broadly expressed on lung cancer cells and is a target for antibody-based therapy.
Tuscano JM, Kato J, Pearson D, Xiong C, Newell L, Ma Y, Gandara DR, O’Donnell RT (2012) CD22 antigen is broadly expressed on lung cancer cells and is a target for antibody-based therapy. Cancer Res 72(21):5556-5565. doi: 10.1158/0008-5472.CAN-12-0173
Summary: The median overall survival of patients with advanced, unresectable, non-small cell lung cancer is 9-12 mos. A potential therapeutic target is CD22, a protein expressed on lung cancer cells. The authors examined the use of the monoclonal antibody HB22.7 as an antitumor agent. To assess internalization of the antibody, it was first incubated with 10 μg/ml Mab-ZAP (Cat. #IT-04) then applied to two different cancer cell lines in culture. Analysis of cell viability demonstrated that CD22 internalized when bound by the antibody-toxin complex, suggesting that targeting CD22 has therapeutic potential.
Related Products: Mab-ZAP (Cat. #IT-04)