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Featured Article: Depletion of syndecan-4+ T lymphocytes by saporin-conjugated DC-HIL alleviates T cell-mediated imflammatory disease
Ariizumi K, Akiyoshi H, Chung JS, Tomiharu M, Cruz Jr PD (2010) Featured Article: Depletion of syndecan-4+ T lymphocytes by saporin-conjugated DC-HIL alleviates T cell-mediated imflammatory disease. Targeting Trends 11(2)
Related Products: Streptavidin-ZAP (Cat. #IT-27)
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Depleting syndecan-4+ T lymphocytes using toxin-bearing dendritic cell-associated heparan sulfate proteoglycan-dependent integrin ligand: A new opportunity for treating activated T cell-driven disease.
Akiyoshi H, Chung JS, Tomihari M, Cruz PD, Jr., Ariizumi K (2010) Depleting syndecan-4+ T lymphocytes using toxin-bearing dendritic cell-associated heparan sulfate proteoglycan-dependent integrin ligand: A new opportunity for treating activated T cell-driven disease. J Immunol 184:3554-3561. doi: 10.4049/jimmunol.0903250
Summary: The dendritic cell-associated heparin sulfate proteoglycan-dependent integrin ligand (DC-HIL) exclusively associates with syndecan-4 (SD-4), which is expressed on some activated T cells. The authors biotinylated DC-HIL and combined it with streptavidin-ZAP (Cat. #IT-27). This complex was then applied to resting or activated T cells in culture at a concentration of 10 µg/ml. Only activated T cells were bound and eliminated.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
Photochemical internalization (PCI): a technology for drug delivery.
Berg K, Weyergang A, Prasmickaite L, Bonsted A, Hogset A, Strand MT, Wagner E, Selbo PK (2010) Photochemical internalization (PCI): a technology for drug delivery. (eds. Gomer C). In: Photodynamic Therapy. Methods in Molecular Biology. 635:133-145. Humana Press, Totowa, NJ. doi: 10.1007/978-1-60761-697-9_10
Summary: This review discusses photochemical internalization (PCI), which is a method used to overcome some of the intracellular barriers to introducing molecules into cancer cells. Some difficulties for such therapies include a low rate of release from endocytic vescicles and degradation of the therapeutic molecule by lysosomal enzymes. The use of streptavidin-ZAP (Cat. #IT-27) with a biotinylated anti-EGF receptor antibody is discussed.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
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T-cell reconstitution without T-cell immunopathology in two models of T-cell-mediated tissue destruction.
Penaloza-MacMaster P, Masopust D, Ahmed R (2009) T-cell reconstitution without T-cell immunopathology in two models of T-cell-mediated tissue destruction. Immunology 128:164-171. doi: 10.1111/j.1365-2567.2009.03080.x
Summary: Although antigen-specific T cells are vital to adaptive immune responses, they also contribute to a variety of diseases. In this work the authors examined the possibility of selectively removing epitope-specific T cells while preserving immune function. Biotinylated MHC class I tetramers were combined with streptavidin-ZAP (Cat. #IT-27) and used in a mouse transferable T-cell-dependent neurological disease model. This technique resulted in a dramatic reduction in targeted antigen specific T cells with no observable bystander toxicity.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
Featured Article: Selective deletion of CD8+ T cells by saporin-coupled MHC class I tetramers
Hess PR, Buntzman AS, Murray SL, Young EF, Frelinger JA (2009) Featured Article: Selective deletion of CD8+ T cells by saporin-coupled MHC class I tetramers. Targeting Trends 10(1)
Related Products: Streptavidin-ZAP (Cat. #IT-27), Saporin Goat Polyclonal, affinity-purified FITC-labeled (Cat. #AB-15APFL)
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Guanidinylated-Neomycin delivers large, bioactive cargo into cells through a heparan sulfate dependent pathway.
Elson-Schwab L, Garner OB, Schuksz M, Esko JD, Tor Y (2007) Guanidinylated-Neomycin delivers large, bioactive cargo into cells through a heparan sulfate dependent pathway. J Biol Chem 282(18):13585-13591. doi: 10.1074/jbc.M700463200
Summary: The uptake of high molecular weight drugs into cells is a stumbling block for some potential therapeutics. Using a neomycin derivative in which guanidinium groups have replaced the ammonium groups, the authors show heparan sulfate-dependent uptake of large molecules. The guanidine-neomycin was biotinylated, and incubated with streptavidin-ZAP (Cat #IT-27). This complex was effective in killing CHO cells in vitro, but was no more effective than streptavidin-ZAP alone on cells lacking heparan sulfate expression, demonstrating specificity.
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Selective deletion of antigen-specific CD8+ T cells by MHC class I tetramers coupled to the type I ribosome-inactivating protein saporin.
Hess PR, Barnes C, Woolard MD, Johnson MD, Cullen JM, Collins EJ, Frelinger JA (2007) Selective deletion of antigen-specific CD8+ T cells by MHC class I tetramers coupled to the type I ribosome-inactivating protein saporin. Blood 109:3300-3307. doi: 10.1182/blood-2006-06-028001
Objective: To discover if pathogenic T cells could be selectively deleted.
Summary: A single injection of the SAP-coupled tetramer eliminated more than 75% of cognate, but not control, T cells. This work demonstrates the therapeutic potential of cytotoxic tetramers to selectively eradicate pathogenic clonotypes while leaving overall T-cell immunity intact.
Usage: Streptavidin-SAP-coupled biotinylated tetramers were administered at low (22.2 pM) or high (66.6 pM) dose. Following the addition of Saporin Goat Polyclonal, affinity-purified FITC-labeled, T cells were subsequently incubated at either 37°C or 4°C, which permitted or prohibited endocytosis, respectively.
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Targeted delivery and enhanced cytotoxicity of cetuximab-saporin by photochemical internalization in EGFR-positive cancer cells.
Yip WL, Weyergang A, Berg K, Tonnesen HH, Selbo PK (2007) Targeted delivery and enhanced cytotoxicity of cetuximab-saporin by photochemical internalization in EGFR-positive cancer cells. Mol Pharm 4(2):241-251. doi: 10.1021/mp060105u
Summary: Photochemical internalization (PCI) releases macromolecules from endocytic vesicles using photosensitizer activation by light. This technique allows the release of endocytosed molecules before degradation occurs in the lysosome. The authors demonstrate the proof-of-concept for this technique by combining biotinylated cetuximab (a chimeric monoclonal antibody to the EGFr) with streptavidin-ZAP (Cat. #IT-27). The conjugate was applied to three different human cancer cell lines, demonstrating enhanced specificity and toxicity against cells expressing the EGFr.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
High-affinity ligand probes of CD22 overcome the threshold set by cis ligands to allow for binding, endocytosis, and killing of B cells.
Collins BE, Blixt O, Han S, Duong B, Li H, Nathan JK, Bovin N, Paulson JC (2006) High-affinity ligand probes of CD22 overcome the threshold set by cis ligands to allow for binding, endocytosis, and killing of B cells. J Immunol 177(5):2994-3003. doi: 10.4049/jimmunol.177.5.2994
Objective: To demonstrate the dynamic equilibrium that exists between CD22 (Siglec-2) and its cis and trans ligands, using a high-affinity multivalent sialoside probe that competes with cis ligands and binds to CD22 on native human and murine B cells.
Summary: The CD22 (Siglec-2) preferred ligand: sequence Siaa2-6Gal that is abundantly expressed on N-linked glycans of B cell glycoproteins. Conjugation of the sialoside probes to the toxin saporin resulted in toxin uptake and toxin-mediated killing of B lymphoma cell lines, suggesting an alternative approach for targeting CD22 for treatment of B cell lymphomas.
Usage: Cytotoxicity assay: BJAB lymphoma cell killing required both the targeting probe and the Streptavidin-ZAP, as no killing was observed in the absence of either.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
Evaluate Potential Targeting Molecules.
Kohls M (2006) Evaluate Potential Targeting Molecules. Nature Methods
Summary: Targeted toxins — targeting agents conjugated to saporin — are widely used to eliminate specific cell populations both in vitro and in vivo. For these molecules to be effective, it is vital that the targeting component of the conjugate specifically binds the cells of interest. A secondary conjugate, Streptavidin-ZAP, has been created by attaching the toxin saporin to streptavidin. The user can combine primary biotinylated material with Streptavidin-ZAP to quickly and economically screen potential targeting molecules for internalization and specificity. Once the appropriate targeting molecule is identified, a direct conjugation with saporin can be performed.
Related Products: Streptavidin-ZAP (Cat. #IT-27)